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

Daehun Park, Yumei Wu, Xinbo Wang, Swetha Gowrishankar, Aaron Baublis and Pietro De Camilli ()
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Daehun Park: Yale University School of Medicine
Yumei Wu: Yale University School of Medicine
Xinbo Wang: Yale University School of Medicine
Swetha Gowrishankar: University of Illinois at Chicago
Aaron Baublis: Harvard T.H. Chan School of Public Health
Pietro De Camilli: Yale University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36081-3

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