Dual interaction of synaptotagmin with μ2- and α-adaptin facilitates clathrin-coated pit nucleation

Volker Haucke, Markus R. Wenk, Edwin R. Chapman, Khashayar Farsad, Pietro De Camilli

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

The synaptic vesicle protein synaptotagmin was proposed to act as a major docking site for the recruitment of clathrin coats implicated in endocytosis, including the recycling of synaptic vesicles. We show here that the C2B domain of synaptotagmin binds μ2- and α-adaptin, two of the four subunits of the endocytic adaptor complex AP.2. μ2 represents the major interacting subunit of AP-2 within this complex. Its binding to synaptotagmin is mediated by a site in subdomain B that is distinct from the binding site for tyrosine-based sorting motifs located in subdomain A. The presence of the C2B domain of synaptotagmin at the surface of liposomes enhances the recruitment of AP-2 and clathrin. Conversely, perturbation of the interaction between synaptotagmin and AP-2 by synprint, the cytoplasmic synaptotagmin-binding domain of N-type calcium channels, inhibits transfertin internalization in living cells. We conclude that a dual interaction of synaptotagmin with the clathrin adaptor AP-2 plays a key physiological role in the nucleation of endocytic clathrin-coated pits.

Original languageEnglish (US)
Pages (from-to)6011-6019
Number of pages9
JournalEMBO Journal
Volume19
Issue number22
StatePublished - Nov 15 2000

Keywords

  • AP-2 adaptor
  • Clathrin
  • Endocytosis
  • Synaptic vesicles
  • Synaptotagmin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Dual interaction of synaptotagmin with μ2- and α-adaptin facilitates clathrin-coated pit nucleation'. Together they form a unique fingerprint.

  • Cite this

    Haucke, V., Wenk, M. R., Chapman, E. R., Farsad, K., & De Camilli, P. (2000). Dual interaction of synaptotagmin with μ2- and α-adaptin facilitates clathrin-coated pit nucleation. EMBO Journal, 19(22), 6011-6019.