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 machineries for synaptic vesicle recycling and cytoskeletal organization. We here report the identification and characterization of SdpII, a ubiquitously expressed isoform of the brain-specific SdpI. Certain splice variants of rat SdpII in other species were named FAP52 and PACSIN 2. SdpII binds dynamin I, synaptojanin, synapsin I, and the neural Wiskott-Aldrich syndrome protein (N-WASP), a stimulator of Arp2/3 induced actin filament nucleation. In neuroendocrine cells, SdpII colocalizes with dynamin, consistent with a role for syndapin in dynamin-mediated endocytic processes. The src homology 3 (SH3) domain of SdpI and -II inhibited receptor-mediated internalization of transferrin, demonstrating syndapin involvement in endocytosis in vivo. Overexpression of full-length syndapins, but not the NH(2)-terminal part or the SH3 domains alone, had a strong effect on cortical actin organization and induced filopodia. This syndapin overexpression phenotype appears to be mediated by the Arp2/3 complex at the cell periphery because it was completely suppressed by coexpression of a cytosolic COOH-terminal fragment of N-WASP. Consistent with a role in actin dynamics, syndapins localized to sites of high actin turnover, such as filopodia tips and lamellipodia. Our results strongly suggest that syndapins link endocytosis and actin dynamics.
Qualmann
B
B
Department of Biochemistry and Biophysics and the Hormone Research Institute, University of California, San Francisco, CA 94143-0534, USA.
Kelly
R B
RB
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis / Q000235:genetics* / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D016716:PC12 Cells; D010750:Phosphoproteins; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics; D051381:Rats; D017386:Sequence Homology, Amino Acid; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D018909:src Homology Domains / Q000235:genetics
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C492182:PACSIN1 protein, human; C120714:PACSIN2 protein, human; C117738:Pacsin1 protein, rat; C492181:Pacsin2 protein, rat; D010750:Phosphoproteins; D020033:Protein Isoforms; D011506:Proteins; C495771:WASL protein, human; C495770:Wasl protein, rat; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C108082:focal adhesion protein, 52-kDa; D020932:Nerve Growth Factor; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins