Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12 cells

Ok Ho Shin, Josep Rizo, Thomas C. Südhof

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 - 2002
Externally publishedYes

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Synaptotagmins
PC12 Cells
Exocytosis
Secretory Vesicles
N-Ethylmaleimide-Sensitive Proteins
Synaptotagmin I
Cell Membrane
Synaptotagmin II
Phospholipids
Protein Binding
Lipids

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12 cells. / Shin, Ok Ho; Rizo, Josep; Südhof, Thomas C.

In: Nature Neuroscience, Vol. 5, No. 7, 2002, p. 649-656.

Research output: Contribution to journalArticle

Shin, Ok Ho ; Rizo, Josep ; Südhof, Thomas C. / Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12 cells. In: Nature Neuroscience. 2002 ; Vol. 5, No. 7. pp. 649-656.
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