Syndapin isoforms participate in receptor-mediated endocytosis and actin organization

Syndapin I (SdpI) interacts with proteins involved in endocytosis and actin dynamics and was therefore proposed to be a molecular link between the mac hineries for synaptic vesicle recycling and cytoskeletal organization. We h ere report the identification and characterization of SdpII, a ubiquitously expressed isoform of the brain-specific SdpI. Certain splice variants of r at SdpII in other species were named FAP52 and PACSIN 2. SdpII binds dynami n I, synaptojanin, synapsin I, and the neural Wiskott-Aldrich syndrome prot ein (N-WASP), a stimulator of Arp2/3 induced actin filament nucleation. In neuroendocrine cells, SdpIII colocalizes with dynamin, consistent with a ro le for syndapin in dynamin-mediated endocytic processes. The src homology 3 (SH3) domain of SdpI and -II inhibited receptor-mediated internalization o f transferrin, demonstrating syndapin involvement in endocytosis in vivo. O verexpression of full-length syndapins, but not the NH2-terminal part or th e SH3 domains alone, had a strong effect on cortical actin organization and induced filopodia. This syndapin overexpression phenotype appears to be me diated by the Arp2/3 complex at the cell periphery because it was completel y suppressed by coexpression of a cytosolic COOH-terminal fragment of N-WAS P. Consistent with a role in actin dynamics, syndapins localized to sites o f high actin turnover, such as filopodia tips and lamellipodia. Our results strongly suggest that syndapins link endocytosis and actin dynamics.