© The Rockefeller University Press,
0021-9525/2000//1047 $5.00
The Journal of Cell Biology, Volume 148, Number 5,
, 2000 1047-1062
Syndapin Isoforms Participate in Receptor-Mediated Endocytosis and Actin Organization
Britta Qualmanna and
Regis B. Kellya
a Department of Biochemistry and Biophysics and the Hormone Research Institute, University of California, San Francisco, California 94143-0534
Department of Biochemistry and Biophysics and the Hormone Research Institute, University of California, 513 Parnassus Avenue, 1090 HSW, San Francisco, CA 94143-0534.(415) 731-3612(415) 476-4095
rkelly{at}biochem.ucsf.edu
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 NH2-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.
Key Words: pheochromocytoma Arp2/3 complex dynamin neural Wiskott-Aldrich syndrome protein filopodia
© 2000 The Rockefeller University Press
Britta Qualmann's present address is Leibnitz Institute for Neurobiology, D-39118 Magdeburg, Germany.
Abbreviations used in this paper: GST, glutathione S-transferase; MBP, maltose binding protein; N-WASP, neural Wiskott-Aldrich syndrome protein; PC12, pheochromocytoma cells; PRD, proline-rich domain; Sdp, syndapin; SH3, src homology 3; VCA, verpolin, homology, cofilin and acidic domains at the COOH terminus of N-WASP; WASP, Wiskott-Aldrich syndrome protein.

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