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Title: An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis
Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these actin and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but actin assembly and productive endocytosis are far more restricted in space and time. Here we describe a mechanism whereby autoinhibition clamps the presynaptic endocytic machinery to limit actin assembly to discrete functional events. We found that collective interactions between theDrosophilaendocytic proteins Nwk/FCHSD2, Dap160/intersectin, and WASp relieve Nwk autoinhibition and promote robust membrane-coupled actin assembly in vitro. Using automated particle tracking to quantify synaptic actin dynamics in vivo, we discovered that Nwk-Dap160 interactions constrain spurious assembly of WASp-dependent actin structures. These interactions also promote synaptic endocytosis, suggesting that autoinhibition both clamps and primes the synaptic endocytic machinery, thereby constraining actin assembly to drive productive membrane remodeling in response to physiological cues.  more » « less
Award ID(s):
2011846
PAR ID:
10506768
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Publisher / Repository:
Elife
Date Published:
Journal Name:
eLife
Volume:
10
ISSN:
2050-084X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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