A proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency.

TitleA proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency.
Publication TypeJournal Article
Year of Publication2019
AuthorsZhang XMin, François U, Silm K, Angelo MFlorencia, Fernandez-Busch MVictoria, Maged M, Martin C, Bernard V, Cordelières FP, Deshors M, Pons S, Maskos U, Bemelmans APierre, Wojcik SM, Mestikawy SEl, Humeau Y, Herzog E
JournalElife
Volume8
Date Published2019 10 30
ISSN2050-084X
Abstract

Glutamate secretion at excitatory synapses is tightly regulated to allow for the precise tuning of synaptic strength. Vesicular Glutamate Transporters (VGLUT) accumulate glutamate into synaptic vesicles (SV) and thereby regulate quantal size. Further, the number of release sites and the release probability of SVs maybe regulated by the organization of active-zone proteins and SV clusters. In the present work, we uncover a mechanism mediating an increased SV clustering through the interaction of VGLUT1 second proline-rich domain, endophilinA1 and intersectin1. This strengthening of SV clusters results in a combined reduction of axonal SV super-pool size and miniature excitatory events frequency. Our findings support a model in which clustered vesicles are held together through multiple weak interactions between Src homology three and proline-rich domains of synaptic proteins. In mammals, VGLUT1 gained a proline-rich sequence that recruits endophilinA1 and turns the transporter into a regulator of SV organization and spontaneous release.

DOI10.7554/eLife.50401
Alternate JournalElife
PubMed ID31663854
PubMed Central IDPMC6861006
Grant ListANR-12-JSV4-0005-01 VGLUT-IQ / / Agence Nationale de la Recherche / International
ANR-10-LABX-43 BRAIN / / Agence Nationale de la Recherche / International
ANR-10-IDEX-03-02 PEPS SV-PIT / / Agence Nationale de la Recherche / International
PSYVGLUT 09-MNPS-033 / / Agence Nationale de la Recherche / International
ANR-10-INBS-04 / / Agence Nationale de la Recherche / International
Erasmus-Mundus European Neuroscience Campus Program / / European Commission / International
FDT20120925288 / / Fondation pour la Recherche Médicale / International
ING20150532192 / / Fondation pour la Recherche Médicale / International