WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation

Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruitin...
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Autor*in:	Gubas, Andrea [verfasserIn] Attridge, Eleanor [verfasserIn] Jefferies, Harold BJ [verfasserIn] Nishimura, Taki [verfasserIn] Razi, Minoo [verfasserIn] Kunzelmann, Simone [verfasserIn] Gilad, Yuval [verfasserIn] Mercer, Thomas J [verfasserIn] Wilson, Michael M [verfasserIn] Kimchi, Adi [verfasserIn] Tooze, Sharon A [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Autophagy Autophagosome Kinase WIPIs Amphipathic Helix

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: EMBO Reports - Nature Publishing Group UK, 2023, 25(2024), 9 vom: 16. Aug., Seite 3789-3811
Übergeordnetes Werk:	volume:25 ; year:2024 ; number:9 ; day:16 ; month:08 ; pages:3789-3811

Links:	Volltext

DOI / URN:	10.1038/s44319-024-00215-5

Katalog-ID:	SPR057282102

Internformat


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100	1		\|a Gubas, Andrea \|e verfasserin \|0 (orcid)0000-0003-4015-0460 \|4 aut
245	1	0	\|a WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation
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520			\|a Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis.
520			\|a Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association.
520			\|a WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis.
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allfields	10.1038/s44319-024-00215-5 doi (DE-627)SPR057282102 (SPR)s44319-024-00215-5-e DE-627 ger DE-627 rakwb eng Gubas, Andrea verfasserin (orcid)0000-0003-4015-0460 aut WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. Autophagy (dpeaa)DE-He213 Autophagosome (dpeaa)DE-He213 Kinase (dpeaa)DE-He213 WIPIs (dpeaa)DE-He213 Amphipathic Helix (dpeaa)DE-He213 Attridge, Eleanor verfasserin (orcid)0009-0004-5799-2159 aut Jefferies, Harold BJ verfasserin aut Nishimura, Taki verfasserin aut Razi, Minoo verfasserin aut Kunzelmann, Simone verfasserin (orcid)0000-0002-2678-0549 aut Gilad, Yuval verfasserin aut Mercer, Thomas J verfasserin aut Wilson, Michael M verfasserin aut Kimchi, Adi verfasserin (orcid)0000-0002-8236-8989 aut Tooze, Sharon A verfasserin (orcid)0000-0002-2182-3116 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 25(2024), 9 vom: 16. Aug., Seite 3789-3811 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811 https://dx.doi.org/10.1038/s44319-024-00215-5 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 9 16 08 3789-3811
spelling	10.1038/s44319-024-00215-5 doi (DE-627)SPR057282102 (SPR)s44319-024-00215-5-e DE-627 ger DE-627 rakwb eng Gubas, Andrea verfasserin (orcid)0000-0003-4015-0460 aut WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. Autophagy (dpeaa)DE-He213 Autophagosome (dpeaa)DE-He213 Kinase (dpeaa)DE-He213 WIPIs (dpeaa)DE-He213 Amphipathic Helix (dpeaa)DE-He213 Attridge, Eleanor verfasserin (orcid)0009-0004-5799-2159 aut Jefferies, Harold BJ verfasserin aut Nishimura, Taki verfasserin aut Razi, Minoo verfasserin aut Kunzelmann, Simone verfasserin (orcid)0000-0002-2678-0549 aut Gilad, Yuval verfasserin aut Mercer, Thomas J verfasserin aut Wilson, Michael M verfasserin aut Kimchi, Adi verfasserin (orcid)0000-0002-8236-8989 aut Tooze, Sharon A verfasserin (orcid)0000-0002-2182-3116 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 25(2024), 9 vom: 16. Aug., Seite 3789-3811 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811 https://dx.doi.org/10.1038/s44319-024-00215-5 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 9 16 08 3789-3811
allfields_unstemmed	10.1038/s44319-024-00215-5 doi (DE-627)SPR057282102 (SPR)s44319-024-00215-5-e DE-627 ger DE-627 rakwb eng Gubas, Andrea verfasserin (orcid)0000-0003-4015-0460 aut WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. Autophagy (dpeaa)DE-He213 Autophagosome (dpeaa)DE-He213 Kinase (dpeaa)DE-He213 WIPIs (dpeaa)DE-He213 Amphipathic Helix (dpeaa)DE-He213 Attridge, Eleanor verfasserin (orcid)0009-0004-5799-2159 aut Jefferies, Harold BJ verfasserin aut Nishimura, Taki verfasserin aut Razi, Minoo verfasserin aut Kunzelmann, Simone verfasserin (orcid)0000-0002-2678-0549 aut Gilad, Yuval verfasserin aut Mercer, Thomas J verfasserin aut Wilson, Michael M verfasserin aut Kimchi, Adi verfasserin (orcid)0000-0002-8236-8989 aut Tooze, Sharon A verfasserin (orcid)0000-0002-2182-3116 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 25(2024), 9 vom: 16. Aug., Seite 3789-3811 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811 https://dx.doi.org/10.1038/s44319-024-00215-5 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 9 16 08 3789-3811
allfieldsGer	10.1038/s44319-024-00215-5 doi (DE-627)SPR057282102 (SPR)s44319-024-00215-5-e DE-627 ger DE-627 rakwb eng Gubas, Andrea verfasserin (orcid)0000-0003-4015-0460 aut WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. Autophagy (dpeaa)DE-He213 Autophagosome (dpeaa)DE-He213 Kinase (dpeaa)DE-He213 WIPIs (dpeaa)DE-He213 Amphipathic Helix (dpeaa)DE-He213 Attridge, Eleanor verfasserin (orcid)0009-0004-5799-2159 aut Jefferies, Harold BJ verfasserin aut Nishimura, Taki verfasserin aut Razi, Minoo verfasserin aut Kunzelmann, Simone verfasserin (orcid)0000-0002-2678-0549 aut Gilad, Yuval verfasserin aut Mercer, Thomas J verfasserin aut Wilson, Michael M verfasserin aut Kimchi, Adi verfasserin (orcid)0000-0002-8236-8989 aut Tooze, Sharon A verfasserin (orcid)0000-0002-2182-3116 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 25(2024), 9 vom: 16. Aug., Seite 3789-3811 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811 https://dx.doi.org/10.1038/s44319-024-00215-5 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 9 16 08 3789-3811
allfieldsSound	10.1038/s44319-024-00215-5 doi (DE-627)SPR057282102 (SPR)s44319-024-00215-5-e DE-627 ger DE-627 rakwb eng Gubas, Andrea verfasserin (orcid)0000-0003-4015-0460 aut WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. Autophagy (dpeaa)DE-He213 Autophagosome (dpeaa)DE-He213 Kinase (dpeaa)DE-He213 WIPIs (dpeaa)DE-He213 Amphipathic Helix (dpeaa)DE-He213 Attridge, Eleanor verfasserin (orcid)0009-0004-5799-2159 aut Jefferies, Harold BJ verfasserin aut Nishimura, Taki verfasserin aut Razi, Minoo verfasserin aut Kunzelmann, Simone verfasserin (orcid)0000-0002-2678-0549 aut Gilad, Yuval verfasserin aut Mercer, Thomas J verfasserin aut Wilson, Michael M verfasserin aut Kimchi, Adi verfasserin (orcid)0000-0002-8236-8989 aut Tooze, Sharon A verfasserin (orcid)0000-0002-2182-3116 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 25(2024), 9 vom: 16. Aug., Seite 3789-3811 (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811 https://dx.doi.org/10.1038/s44319-024-00215-5 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2050 GBV_ILN_2118 GBV_ILN_2153 GBV_ILN_2472 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2024 9 16 08 3789-3811
language	English
source	Enthalten in EMBO Reports 25(2024), 9 vom: 16. Aug., Seite 3789-3811 volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811
sourceStr	Enthalten in EMBO Reports 25(2024), 9 vom: 16. Aug., Seite 3789-3811 volume:25 year:2024 number:9 day:16 month:08 pages:3789-3811
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Autophagy Autophagosome Kinase WIPIs Amphipathic Helix
isfreeaccess_bool	true
container_title	EMBO Reports
authorswithroles_txt_mv	Gubas, Andrea @@aut@@ Attridge, Eleanor @@aut@@ Jefferies, Harold BJ @@aut@@ Nishimura, Taki @@aut@@ Razi, Minoo @@aut@@ Kunzelmann, Simone @@aut@@ Gilad, Yuval @@aut@@ Mercer, Thomas J @@aut@@ Wilson, Michael M @@aut@@ Kimchi, Adi @@aut@@ Tooze, Sharon A @@aut@@
publishDateDaySort_date	2024-08-16T00:00:00Z
hierarchy_top_id	320645622
id	SPR057282102
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR057282102</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240911064707.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240911s2024 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s44319-024-00215-5</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR057282102</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s44319-024-00215-5-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Gubas, Andrea</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0003-4015-0460</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2024</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. 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author	Gubas, Andrea
spellingShingle	Gubas, Andrea misc Autophagy misc Autophagosome misc Kinase misc WIPIs misc Amphipathic Helix WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation
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topic_title	WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation Autophagy (dpeaa)DE-He213 Autophagosome (dpeaa)DE-He213 Kinase (dpeaa)DE-He213 WIPIs (dpeaa)DE-He213 Amphipathic Helix (dpeaa)DE-He213
topic	misc Autophagy misc Autophagosome misc Kinase misc WIPIs misc Amphipathic Helix
topic_unstemmed	misc Autophagy misc Autophagosome misc Kinase misc WIPIs misc Amphipathic Helix
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title	WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation
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title_full	WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation
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author_browse	Gubas, Andrea Attridge, Eleanor Jefferies, Harold BJ Nishimura, Taki Razi, Minoo Kunzelmann, Simone Gilad, Yuval Mercer, Thomas J Wilson, Michael M Kimchi, Adi Tooze, Sharon A
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title_sort	wipi2b recruitment to phagophores and atg16l1 binding are regulated by ulk1 phosphorylation
title_auth	WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation
abstract	Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. © The Author(s) 2024
abstractGer	Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. © The Author(s) 2024
abstract_unstemmed	Abstract One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis. Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association. WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. © The Author(s) 2024
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container_issue	9
title_short	WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation
url	https://dx.doi.org/10.1038/s44319-024-00215-5
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author2	Attridge, Eleanor Jefferies, Harold BJ Nishimura, Taki Razi, Minoo Kunzelmann, Simone Gilad, Yuval Mercer, Thomas J Wilson, Michael M Kimchi, Adi Tooze, Sharon A
author2Str	Attridge, Eleanor Jefferies, Harold BJ Nishimura, Taki Razi, Minoo Kunzelmann, Simone Gilad, Yuval Mercer, Thomas J Wilson, Michael M Kimchi, Adi Tooze, Sharon A
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up_date	2024-09-11T04:48:44.248Z
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WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Synopsis WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis. WIPI2b is a novel ULK1 substrate, phosphorylated at S284 and S68.Phosphorylation at S68 reduces WIPI2b-ATG16L1 association.Phosphorylation at S284 prevents the formation of WIPI2bs amphipathic helix in the 6CD loop, likely disrupting membrane association.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">WIPI2b is a novel ULK1 substrate which is phosphorylated at two key sites, S68 and S284. The phosphorylation at S68 and S284 of WIPI2b regulates its function at the phagophore disrupting the association with ATG16L1 and membranes. These results sheds light on the complex process of autophagosome biogenesis.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Autophagy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Autophagosome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kinase</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">WIPIs</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Amphipathic Helix</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Attridge, Eleanor</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0009-0004-5799-2159</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jefferies, Harold BJ</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Nishimura, Taki</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Razi, Minoo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kunzelmann, Simone</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-2678-0549</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gilad, Yuval</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mercer, Thomas J</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wilson, Michael M</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kimchi, Adi</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-8236-8989</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tooze, Sharon A</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-2182-3116</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">EMBO Reports</subfield><subfield code="d">Nature Publishing Group UK, 2023</subfield><subfield code="g">25(2024), 9 vom: 16. 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WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation

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