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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Main Authors: Lauren Kershberg, Aditi Banerjee, Pascal S Kaeser
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-12-01
Series:eLife
Subjects:
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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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
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AT aditibanerjee proteincompositionofaxonaldopaminereleasesitesinthestriatum
AT pascalskaeser proteincompositionofaxonaldopaminereleasesitesinthestriatum