Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron...
Ausführliche Beschreibung
Autor*in: |
Bontempi, Leonardo [verfasserIn] |
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E-Artikel |
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Englisch |
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2017transfer abstract |
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Umfang: |
12 |
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Übergeordnetes Werk: |
Enthalten in: Temperature-dependence laws of absorption line shape parameters of the CO - Wilzewski, J.S. ELSEVIER, 2017, ENP : the journal of the European College of Neuropsychopharmacology, Amsterdam |
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Übergeordnetes Werk: |
volume:27 ; year:2017 ; number:4 ; pages:313-324 ; extent:12 |
Links: |
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DOI / URN: |
10.1016/j.euroneuro.2017.01.015 |
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ELV025399993 |
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245 | 1 | 0 | |a Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity |
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520 | |a Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. | ||
520 | |a Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. | ||
650 | 7 | |a Dopamine |2 Elsevier | |
650 | 7 | |a D3 Receptor |2 Elsevier | |
650 | 7 | |a Heteromerization |2 Elsevier | |
650 | 7 | |a Plasticity |2 Elsevier | |
650 | 7 | |a Nicotinic receptor |2 Elsevier | |
650 | 7 | |a Nicotine |2 Elsevier | |
700 | 1 | |a Savoia, Paola |4 oth | |
700 | 1 | |a Bono, Federica |4 oth | |
700 | 1 | |a Fiorentini, Chiara |4 oth | |
700 | 1 | |a Missale, Cristina |4 oth | |
773 | 0 | 8 | |i Enthalten in |n Elsevier |a Wilzewski, J.S. ELSEVIER |t Temperature-dependence laws of absorption line shape parameters of the CO |d 2017 |d ENP : the journal of the European College of Neuropsychopharmacology |g Amsterdam |w (DE-627)ELV000200816 |
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10.1016/j.euroneuro.2017.01.015 doi GBVA2017014000005.pica (DE-627)ELV025399993 (ELSEVIER)S0924-977X(17)30048-2 DE-627 ger DE-627 rakwb eng 150 610 150 DE-600 610 DE-600 530 VZ 33.00 bkl Bontempi, Leonardo verfasserin aut Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity 2017transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Dopamine Elsevier D3 Receptor Elsevier Heteromerization Elsevier Plasticity Elsevier Nicotinic receptor Elsevier Nicotine Elsevier Savoia, Paola oth Bono, Federica oth Fiorentini, Chiara oth Missale, Cristina oth Enthalten in Elsevier Wilzewski, J.S. ELSEVIER Temperature-dependence laws of absorption line shape parameters of the CO 2017 ENP : the journal of the European College of Neuropsychopharmacology Amsterdam (DE-627)ELV000200816 volume:27 year:2017 number:4 pages:313-324 extent:12 https://doi.org/10.1016/j.euroneuro.2017.01.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.00 Physik: Allgemeines VZ AR 27 2017 4 313-324 12 045F 150 |
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10.1016/j.euroneuro.2017.01.015 doi GBVA2017014000005.pica (DE-627)ELV025399993 (ELSEVIER)S0924-977X(17)30048-2 DE-627 ger DE-627 rakwb eng 150 610 150 DE-600 610 DE-600 530 VZ 33.00 bkl Bontempi, Leonardo verfasserin aut Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity 2017transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Dopamine Elsevier D3 Receptor Elsevier Heteromerization Elsevier Plasticity Elsevier Nicotinic receptor Elsevier Nicotine Elsevier Savoia, Paola oth Bono, Federica oth Fiorentini, Chiara oth Missale, Cristina oth Enthalten in Elsevier Wilzewski, J.S. ELSEVIER Temperature-dependence laws of absorption line shape parameters of the CO 2017 ENP : the journal of the European College of Neuropsychopharmacology Amsterdam (DE-627)ELV000200816 volume:27 year:2017 number:4 pages:313-324 extent:12 https://doi.org/10.1016/j.euroneuro.2017.01.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.00 Physik: Allgemeines VZ AR 27 2017 4 313-324 12 045F 150 |
allfields_unstemmed |
10.1016/j.euroneuro.2017.01.015 doi GBVA2017014000005.pica (DE-627)ELV025399993 (ELSEVIER)S0924-977X(17)30048-2 DE-627 ger DE-627 rakwb eng 150 610 150 DE-600 610 DE-600 530 VZ 33.00 bkl Bontempi, Leonardo verfasserin aut Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity 2017transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Dopamine Elsevier D3 Receptor Elsevier Heteromerization Elsevier Plasticity Elsevier Nicotinic receptor Elsevier Nicotine Elsevier Savoia, Paola oth Bono, Federica oth Fiorentini, Chiara oth Missale, Cristina oth Enthalten in Elsevier Wilzewski, J.S. ELSEVIER Temperature-dependence laws of absorption line shape parameters of the CO 2017 ENP : the journal of the European College of Neuropsychopharmacology Amsterdam (DE-627)ELV000200816 volume:27 year:2017 number:4 pages:313-324 extent:12 https://doi.org/10.1016/j.euroneuro.2017.01.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.00 Physik: Allgemeines VZ AR 27 2017 4 313-324 12 045F 150 |
allfieldsGer |
10.1016/j.euroneuro.2017.01.015 doi GBVA2017014000005.pica (DE-627)ELV025399993 (ELSEVIER)S0924-977X(17)30048-2 DE-627 ger DE-627 rakwb eng 150 610 150 DE-600 610 DE-600 530 VZ 33.00 bkl Bontempi, Leonardo verfasserin aut Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity 2017transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Dopamine Elsevier D3 Receptor Elsevier Heteromerization Elsevier Plasticity Elsevier Nicotinic receptor Elsevier Nicotine Elsevier Savoia, Paola oth Bono, Federica oth Fiorentini, Chiara oth Missale, Cristina oth Enthalten in Elsevier Wilzewski, J.S. ELSEVIER Temperature-dependence laws of absorption line shape parameters of the CO 2017 ENP : the journal of the European College of Neuropsychopharmacology Amsterdam (DE-627)ELV000200816 volume:27 year:2017 number:4 pages:313-324 extent:12 https://doi.org/10.1016/j.euroneuro.2017.01.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.00 Physik: Allgemeines VZ AR 27 2017 4 313-324 12 045F 150 |
allfieldsSound |
10.1016/j.euroneuro.2017.01.015 doi GBVA2017014000005.pica (DE-627)ELV025399993 (ELSEVIER)S0924-977X(17)30048-2 DE-627 ger DE-627 rakwb eng 150 610 150 DE-600 610 DE-600 530 VZ 33.00 bkl Bontempi, Leonardo verfasserin aut Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity 2017transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. Dopamine Elsevier D3 Receptor Elsevier Heteromerization Elsevier Plasticity Elsevier Nicotinic receptor Elsevier Nicotine Elsevier Savoia, Paola oth Bono, Federica oth Fiorentini, Chiara oth Missale, Cristina oth Enthalten in Elsevier Wilzewski, J.S. ELSEVIER Temperature-dependence laws of absorption line shape parameters of the CO 2017 ENP : the journal of the European College of Neuropsychopharmacology Amsterdam (DE-627)ELV000200816 volume:27 year:2017 number:4 pages:313-324 extent:12 https://doi.org/10.1016/j.euroneuro.2017.01.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 33.00 Physik: Allgemeines VZ AR 27 2017 4 313-324 12 045F 150 |
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Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity |
abstract |
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. |
abstractGer |
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. |
abstract_unstemmed |
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer2 (BRET2) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET2 showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET2 signal generated by D3R-GFP2 and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine. |
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