Syndapins integrate N-WASP in receptor-mediated endocytosis

Abstract

Syndapins are potential links between the cortical actin cytoskeleton and endocytosis because this family of dynamin‐associated proteins can also interact with the Arp2/3 complex activator N‐WASP. Here we provide evidence for involvement of N‐WASP interactions in receptor‐mediated endocytosis. We reveal that the observed dominant‐negative effects of N‐WASP are dependent exclusively on the proline‐rich domain, the binding interface of syndapins. Our results therefore suggest that syndapins integrate N‐WASP functions in endocytosis. Both proteins co‐localize in neuronal cells. Consistent with a crucial role for syndapins in endocytic uptake, co‐overexpression of syndapins rescued the endocytosis block caused by N‐WASP. An in vivo reconstitution of the syndapin–N‐WASP interaction at cellular membranes triggered local actin polymerization. Depletion of endogenous N‐WASP by sequestering it to mitochondria or by introducing anti‐N‐WASP antibodies impaired endocytosis. Our data suggest that syndapins may act as important coordinators of N‐WASP and dynamin functions during the different steps of receptor‐mediated endocytosis and that local actin polymerization induced by syndapin–N‐WASP interactions may be a mechanism supporting clathrin‐coated vesicle detachment and movement away from the plasma membrane.