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

Xiao Min Zhang | Urielle François | Kätlin Silm | Maria Florencia Angelo | Maria Victoria Fernandez-Busch | Mona Maged | Christelle Martin | Véronique Bernard | Fabrice P Cordelières | Melissa Deshors | Stéphanie Pons | Uwe Maskos | Alexis Pierre Bemelmans | Sonja M Wojcik | Salah El Mestikawy | Yann Humeau | Etienne Herzog
eLife | 2019

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.

Pubmed ID: 31663854

Associated grants

  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-12-JSV4-0005-01 VGLUT-IQ
  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-10-LABX-43 BRAIN
  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-10-IDEX-03-02 PEPS SV-PIT
  • Agency: Agence Nationale de la Recherche, International
    Id: PSYVGLUT 09-MNPS-033
  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-10-INBS-04
  • Agency: European Commission, International
    Id: Erasmus-Mundus European Neuroscience Campus Program
  • Agency: Fondation pour la Recherche Médicale, International
    Id: FDT20120925288
  • Agency: Fondation pour la Recherche Médicale, International
    Id: ING20150532192

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