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Publication : Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates.

First Author  Park D Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  455
PubMed ID  36709207 Mgi Jnum  J:333104
Mgi Id  MGI:7431904 Doi  10.1038/s41467-023-36081-3
Citation  Park D, et al. (2023) Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates. Nat Commun 14(1):455
abstractText  Ectopic expression in fibroblasts of synapsin 1 and synaptophysin is sufficient to generate condensates of vesicles highly reminiscent of synaptic vesicle (SV) clusters and with liquid-like properties. Here we show that unlike synaptophysin, other major integral SV membrane proteins fail to form condensates with synapsin, but co-assemble into the clusters formed by synaptophysin and synapsin in this ectopic expression system. Another vesicle membrane protein, ATG9A, undergoes activity-dependent exo-endocytosis at synapses, raising questions about the relation of ATG9A traffic to the traffic of SVs. We find that both in fibroblasts and in nerve terminals ATG9A does not co-assemble into synaptophysin-positive vesicle condensates but localizes on a distinct class of vesicles that also assembles with synapsin but into a distinct phase. Our findings suggest that ATG9A undergoes differential sorting relative to SV proteins and also point to a dual role of synapsin in controlling clustering at synapses of SVs and ATG9A vesicles.
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