Functional and biochemical analysis of the C2 domains of synaptotagmin IV

David M. Thomas, Gregory D. Ferguson, Harvey R. Herschman, Lisa Elferink

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Synaptotagmins (Syts) are a family of vesicle proteins that have been implicated in both regulated neurosecretion and general membrane trafficking. Calcium-dependent interactions mediated through their C2 domains are proposed to contribute to the mechanism by which Syts trigger calcium-dependent neurotransmitter release. Syt IV is a novel member of the Syt family that is induced by cell depolarization and has a rapid rate of synthesis and a short half-life. Moreover, the C2A domain of Syt IV does not bind calcium. We have examined the biochemical and functional properties of the C2 domains of Syt IV. Consistent with its non-calcium binding properties, the C2A domain of Syt IV binds syntaxin isoforms in a calcium-independent manner. In neuroendocrine pheochromocytoma (PC12) cells, Syt IV colocalizes with Syt I in the tips of the neurites. Microinjection of the C2A domain reveals that calcium- independent interactions mediated through this domain of Syt IV inhibit calcium-mediated neurotransmitter release from PC12 cells. Conversely, the C2B domain of Syt IV contains calcium binding properties, which permit homo- oligomerization as well as hetero-oligomerization with Syt I. Our observation that different combinatorial interactions exist between Syt and syntaxin isoforms, coupled with the calcium stimulated hetero-oligomerization of Syt isoforms, suggests that the secretory machinery contains a vast repertoire of biochemical properties for sensing calcium and regulating neurotransmitter release accordingly.

Original languageEnglish (US)
Pages (from-to)2285-2295
Number of pages11
JournalMolecular Biology of the Cell
Volume10
Issue number7
StatePublished - Jul 1999
Externally publishedYes

Fingerprint

Synaptotagmins
Calcium
Qa-SNARE Proteins
Neurotransmitter Agents
Protein Isoforms
PC12 Cells
Neurosecretion
C2 Domains
Microinjections
Pheochromocytoma
Neurites
Half-Life

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Thomas, D. M., Ferguson, G. D., Herschman, H. R., & Elferink, L. (1999). Functional and biochemical analysis of the C2 domains of synaptotagmin IV. Molecular Biology of the Cell, 10(7), 2285-2295.

Functional and biochemical analysis of the C2 domains of synaptotagmin IV. / Thomas, David M.; Ferguson, Gregory D.; Herschman, Harvey R.; Elferink, Lisa.

In: Molecular Biology of the Cell, Vol. 10, No. 7, 07.1999, p. 2285-2295.

Research output: Contribution to journalArticle

Thomas, DM, Ferguson, GD, Herschman, HR & Elferink, L 1999, 'Functional and biochemical analysis of the C2 domains of synaptotagmin IV', Molecular Biology of the Cell, vol. 10, no. 7, pp. 2285-2295.
Thomas, David M. ; Ferguson, Gregory D. ; Herschman, Harvey R. ; Elferink, Lisa. / Functional and biochemical analysis of the C2 domains of synaptotagmin IV. In: Molecular Biology of the Cell. 1999 ; Vol. 10, No. 7. pp. 2285-2295.
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