Protein composition of axonal dopamine release sites in the striatum
Dopamine is an important modulator of cognition and movement. We recently found that evoked dopamine secretion is fast and relies on active zone-like release sites. Here, we used in vivo biotin identification (iBioID) proximity proteomics in mouse striatum to assess which proteins are present at the...
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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2022-12-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/83018 |
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author | Lauren Kershberg Aditi Banerjee Pascal S Kaeser |
author_facet | Lauren Kershberg Aditi Banerjee Pascal S Kaeser |
author_sort | Lauren Kershberg |
collection | DOAJ |
description | Dopamine is an important modulator of cognition and movement. We recently found that evoked dopamine secretion is fast and relies on active zone-like release sites. Here, we used in vivo biotin identification (iBioID) proximity proteomics in mouse striatum to assess which proteins are present at these sites. Using three release site baits, we identified proteins that are enriched over the general dopamine axonal protein content, and they fell into several categories, including active zone, Ca2+ regulatory, and synaptic vesicle proteins. We also detected many proteins not previously associated with vesicular exocytosis. Knockout of the presynaptic organizer protein RIM strongly decreased the hit number obtained with iBioID, while Synaptotagmin-1 knockout did not. α-Synuclein, a protein linked to Parkinson’s disease, was enriched at release sites, and its enrichment was lost in both tested mutants. We conclude that RIM organizes scaffolded dopamine release sites and provide a proteomic assessment of the composition of these sites. |
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id | doaj.art-1e7be787b600464f8576c36bb8162e0e |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-10T09:38:19Z |
publishDate | 2022-12-01 |
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spelling | doaj.art-1e7be787b600464f8576c36bb8162e0e2023-02-17T16:11:21ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.83018Protein composition of axonal dopamine release sites in the striatumLauren Kershberg0https://orcid.org/0000-0002-5676-4160Aditi Banerjee1https://orcid.org/0000-0003-2016-0717Pascal S Kaeser2https://orcid.org/0000-0002-1558-1958Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDopamine is an important modulator of cognition and movement. We recently found that evoked dopamine secretion is fast and relies on active zone-like release sites. Here, we used in vivo biotin identification (iBioID) proximity proteomics in mouse striatum to assess which proteins are present at these sites. Using three release site baits, we identified proteins that are enriched over the general dopamine axonal protein content, and they fell into several categories, including active zone, Ca2+ regulatory, and synaptic vesicle proteins. We also detected many proteins not previously associated with vesicular exocytosis. Knockout of the presynaptic organizer protein RIM strongly decreased the hit number obtained with iBioID, while Synaptotagmin-1 knockout did not. α-Synuclein, a protein linked to Parkinson’s disease, was enriched at release sites, and its enrichment was lost in both tested mutants. We conclude that RIM organizes scaffolded dopamine release sites and provide a proteomic assessment of the composition of these sites.https://elifesciences.org/articles/83018dopaminestriatumactive zoneRIMSsecretionexocytosis |
spellingShingle | Lauren Kershberg Aditi Banerjee Pascal S Kaeser Protein composition of axonal dopamine release sites in the striatum eLife dopamine striatum active zone RIMS secretion exocytosis |
title | Protein composition of axonal dopamine release sites in the striatum |
title_full | Protein composition of axonal dopamine release sites in the striatum |
title_fullStr | Protein composition of axonal dopamine release sites in the striatum |
title_full_unstemmed | Protein composition of axonal dopamine release sites in the striatum |
title_short | Protein composition of axonal dopamine release sites in the striatum |
title_sort | protein composition of axonal dopamine release sites in the striatum |
topic | dopamine striatum active zone RIMS secretion exocytosis |
url | https://elifesciences.org/articles/83018 |
work_keys_str_mv | AT laurenkershberg proteincompositionofaxonaldopaminereleasesitesinthestriatum AT aditibanerjee proteincompositionofaxonaldopaminereleasesitesinthestriatum AT pascalskaeser proteincompositionofaxonaldopaminereleasesitesinthestriatum |