Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review

Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Kaushal, Jyoti B. [verfasserIn] Batra, Surinder K. Rachagani, Satyanarayana

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Hedgehog Cholesterol Smo Ptch1 Plasma membrane Canonical signaling Non-canonical signaling

Anmerkung:	© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022

Übergeordnetes Werk:	Enthalten in: Cellular and molecular life sciences - Cham (ZG) : Springer International Publishing AG, 1997, 79(2022), 5 vom: 29. Apr.
Übergeordnetes Werk:	volume:79 ; year:2022 ; number:5 ; day:29 ; month:04

Links:	Volltext

DOI / URN:	10.1007/s00018-022-04233-1

Katalog-ID:	SPR046869840

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allfields	10.1007/s00018-022-04233-1 doi (DE-627)SPR046869840 (SPR)s00018-022-04233-1-e DE-627 ger DE-627 rakwb eng Kaushal, Jyoti B. verfasserin aut Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. Hedgehog (dpeaa)DE-He213 Cholesterol (dpeaa)DE-He213 Smo (dpeaa)DE-He213 Ptch1 (dpeaa)DE-He213 Plasma membrane (dpeaa)DE-He213 Canonical signaling (dpeaa)DE-He213 Non-canonical signaling (dpeaa)DE-He213 Batra, Surinder K. aut Rachagani, Satyanarayana (orcid)0000-0003-3949-8566 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 79(2022), 5 vom: 29. Apr. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:79 year:2022 number:5 day:29 month:04 https://dx.doi.org/10.1007/s00018-022-04233-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 79 2022 5 29 04
spelling	10.1007/s00018-022-04233-1 doi (DE-627)SPR046869840 (SPR)s00018-022-04233-1-e DE-627 ger DE-627 rakwb eng Kaushal, Jyoti B. verfasserin aut Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. Hedgehog (dpeaa)DE-He213 Cholesterol (dpeaa)DE-He213 Smo (dpeaa)DE-He213 Ptch1 (dpeaa)DE-He213 Plasma membrane (dpeaa)DE-He213 Canonical signaling (dpeaa)DE-He213 Non-canonical signaling (dpeaa)DE-He213 Batra, Surinder K. aut Rachagani, Satyanarayana (orcid)0000-0003-3949-8566 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 79(2022), 5 vom: 29. Apr. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:79 year:2022 number:5 day:29 month:04 https://dx.doi.org/10.1007/s00018-022-04233-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 79 2022 5 29 04
allfields_unstemmed	10.1007/s00018-022-04233-1 doi (DE-627)SPR046869840 (SPR)s00018-022-04233-1-e DE-627 ger DE-627 rakwb eng Kaushal, Jyoti B. verfasserin aut Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. Hedgehog (dpeaa)DE-He213 Cholesterol (dpeaa)DE-He213 Smo (dpeaa)DE-He213 Ptch1 (dpeaa)DE-He213 Plasma membrane (dpeaa)DE-He213 Canonical signaling (dpeaa)DE-He213 Non-canonical signaling (dpeaa)DE-He213 Batra, Surinder K. aut Rachagani, Satyanarayana (orcid)0000-0003-3949-8566 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 79(2022), 5 vom: 29. Apr. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:79 year:2022 number:5 day:29 month:04 https://dx.doi.org/10.1007/s00018-022-04233-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 79 2022 5 29 04
allfieldsGer	10.1007/s00018-022-04233-1 doi (DE-627)SPR046869840 (SPR)s00018-022-04233-1-e DE-627 ger DE-627 rakwb eng Kaushal, Jyoti B. verfasserin aut Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. Hedgehog (dpeaa)DE-He213 Cholesterol (dpeaa)DE-He213 Smo (dpeaa)DE-He213 Ptch1 (dpeaa)DE-He213 Plasma membrane (dpeaa)DE-He213 Canonical signaling (dpeaa)DE-He213 Non-canonical signaling (dpeaa)DE-He213 Batra, Surinder K. aut Rachagani, Satyanarayana (orcid)0000-0003-3949-8566 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 79(2022), 5 vom: 29. Apr. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:79 year:2022 number:5 day:29 month:04 https://dx.doi.org/10.1007/s00018-022-04233-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 79 2022 5 29 04
allfieldsSound	10.1007/s00018-022-04233-1 doi (DE-627)SPR046869840 (SPR)s00018-022-04233-1-e DE-627 ger DE-627 rakwb eng Kaushal, Jyoti B. verfasserin aut Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. Hedgehog (dpeaa)DE-He213 Cholesterol (dpeaa)DE-He213 Smo (dpeaa)DE-He213 Ptch1 (dpeaa)DE-He213 Plasma membrane (dpeaa)DE-He213 Canonical signaling (dpeaa)DE-He213 Non-canonical signaling (dpeaa)DE-He213 Batra, Surinder K. aut Rachagani, Satyanarayana (orcid)0000-0003-3949-8566 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 79(2022), 5 vom: 29. Apr. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:79 year:2022 number:5 day:29 month:04 https://dx.doi.org/10.1007/s00018-022-04233-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 79 2022 5 29 04
language	English
source	Enthalten in Cellular and molecular life sciences 79(2022), 5 vom: 29. Apr. volume:79 year:2022 number:5 day:29 month:04
sourceStr	Enthalten in Cellular and molecular life sciences 79(2022), 5 vom: 29. Apr. volume:79 year:2022 number:5 day:29 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Hedgehog Cholesterol Smo Ptch1 Plasma membrane Canonical signaling Non-canonical signaling
isfreeaccess_bool	false
container_title	Cellular and molecular life sciences
authorswithroles_txt_mv	Kaushal, Jyoti B. @@aut@@ Batra, Surinder K. @@aut@@ Rachagani, Satyanarayana @@aut@@
publishDateDaySort_date	2022-04-29T00:00:00Z
hierarchy_top_id	253390524
id	SPR046869840
language_de	englisch
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author	Kaushal, Jyoti B.
spellingShingle	Kaushal, Jyoti B. misc Hedgehog misc Cholesterol misc Smo misc Ptch1 misc Plasma membrane misc Canonical signaling misc Non-canonical signaling Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review
authorStr	Kaushal, Jyoti B.
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topic_title	Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review Hedgehog (dpeaa)DE-He213 Cholesterol (dpeaa)DE-He213 Smo (dpeaa)DE-He213 Ptch1 (dpeaa)DE-He213 Plasma membrane (dpeaa)DE-He213 Canonical signaling (dpeaa)DE-He213 Non-canonical signaling (dpeaa)DE-He213
topic	misc Hedgehog misc Cholesterol misc Smo misc Ptch1 misc Plasma membrane misc Canonical signaling misc Non-canonical signaling
topic_unstemmed	misc Hedgehog misc Cholesterol misc Smo misc Ptch1 misc Plasma membrane misc Canonical signaling misc Non-canonical signaling
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title	Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review
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title_full	Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review
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author_browse	Kaushal, Jyoti B. Batra, Surinder K. Rachagani, Satyanarayana
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title_sort	hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review
title_auth	Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review
abstract	Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022
abstractGer	Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022
abstract_unstemmed	Abstract Hedgehog (Hh) signaling is evolutionarily conserved and plays an instructional role in embryonic morphogenesis, organogenesis in various animals, and the central nervous system organization. Multiple feedback mechanisms dynamically regulate this pathway in a spatiotemporal and context-dependent manner to confer differential patterns in cell fate determination. Hh signaling is complex due to canonical and non-canonical mechanisms coordinating cell–cell communication. In addition, studies have demonstrated a regulatory framework of Hh signaling and shown that cholesterol is vital for Hh ligand biogenesis, signal generation, and transduction from the cell surface to intracellular space. Studies have shown the importance of a specific cholesterol pool, termed accessible cholesterol, which serves as a second messenger, conveying signals between smoothened (Smo) and patched 1 (Ptch1) across the plasma and ciliary membranes. Remarkably, recent high-resolution structural and molecular studies shed new light on the interplay between Hh signaling and cholesterol in membrane biology. These studies elucidated novel mechanistic insight into the release and dispersal of cholesterol-anchored Hh and the basis of Hh recognition by Ptch1. Additionally, the putative model of Smo activation by cholesterol binding and/or modification and Ptch1 antagonization of Smo has been explicated. However, the coupling mechanism of Hh signaling and cholesterol offered a new regulatory principle in cell biology: how effector molecules of the Hh signal network react to and remodel cholesterol accessibility in the membrane and selectively activate Hh signaling proteins thereof. Recognizing the biological importance of cholesterol in Hh signaling activation and transduction opens the door for translational research to develop novel therapeutic strategies. This review looks in-depth at canonical and non-canonical Hh signaling and the distinct proposed model of cholesterol-mediated regulation of Hh signaling components, facilitating a more sophisticated understanding of the Hh signal network and cholesterol biology. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022
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title_short	Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review
url	https://dx.doi.org/10.1007/s00018-022-04233-1
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author2	Batra, Surinder K. Rachagani, Satyanarayana
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doi_str	10.1007/s00018-022-04233-1
up_date	2024-07-04T00:48:26.215Z
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