Synaptotagmin function in dense core vesicle exocytosis studied in cracked pc12 cells

Ok Ho Shin, Jose Rizo-Rey, Thomas C. Südhof

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Ca2+-triggered dense-core vesicle exocytosis in PC12 cells does not require vesicular synaptotagmins 1 and 2, but may use plasma membrane synaptotagmins 3 and 7 as Ca2+ sensors. In support of this hypothesis, C2 domains from the plasma membrane but not vesicular synaptotagmins inhibit PC12 cell exocytosis. Ca2+ induces binding of both plasma membrane and vesicular synaptotagmins to phospholipids and SNAREs (soluble N-ethylmaleimide-sensitive attachment protein receptors), although with distinct apparent Ca2+ affinities. Here we used gain-of-function C2-domain mutants of synaptotagmin 1 and loss-of-function C2-domain mutants of synaptotagmin 7 to examine how synaptotagmins function in dense-core vesicle exocytosis. Our data indicate that phospholipid- but not SNARE-binding by plasma membrane synaptotagmins is the primary determinant of Ca2+-triggered dense-core vesicle exocytosis. These results support a general lipid-based mechanism of action of synaptotagmins in exocytosis, with the specificity of various synaptotagmins for different types of fusion governed by their differential localizations and Ca2+ affinities.

Original languageEnglish (US)
Pages (from-to)649-656
Number of pages8
JournalNature neuroscience
Volume5
Issue number7
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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