Association of neuronal calcium channels with modular adaptor proteins

Anton Maximov, Thomas C. Südhof, Ilya Bezprozvanny

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

Presynaptic voltage-gated calcium (Ca2+) channels mediate Ca2+ influx into the presynaptic terminal that triggers synaptic vesicle fusion and neurotransmitter release. The immediate proximity of Ca2+ channels to the synaptic vesicle release apparatus is critical for rapid and efficient synaptic transmission. In a series of biochemical experiments, we demonstrate a specific association of the cytosolic carboxyl terminus of the N-type Ca2+ channel pore-forming α(1B) subunit with the modular adaptor proteins Mint1 and CASK. The carboxyl termini of α(1B) bind to the first PDZ domain of Mint1 (Mint1-1). The proline-rich region present in the carboxyl termini of α(1B) binds to the SH3 domain of CASK. Mint1-1 is specific for the E/D-X- W-C/S-COOH consensus, which defines a novel class of PDZ domains (class III). The Mint1-1 PDZ domain-binding motif is present only in the 'long' carboxyl- terminal splice variants of N-type (α(1B)) and P/Q-type (α(1A)) Ca2+ channels, but not in R-type (α(1E)) or L-type (α(1C)) Ca2+ channels. Our results directly link presynaptic Ca2+ channels to a macromolecular complex formed by modular adaptor proteins at synaptic junction and advance our understanding of coupling between cell adhesion and synaptic vesicle exocytosis.

Original languageEnglish (US)
Pages (from-to)24453-24456
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number35
DOIs
StatePublished - Aug 27 1999

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PDZ Domains
Synaptic Vesicles
Calcium Channels
Macromolecular Substances
Cell adhesion
Proline
Neurotransmitter Agents
Proteins
Fusion reactions
src Homology Domains
Exocytosis
Presynaptic Terminals
Calcium
Cell Adhesion
Synaptic Transmission
Electric potential
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Association of neuronal calcium channels with modular adaptor proteins. / Maximov, Anton; Südhof, Thomas C.; Bezprozvanny, Ilya.

In: Journal of Biological Chemistry, Vol. 274, No. 35, 27.08.1999, p. 24453-24456.

Research output: Contribution to journalArticle

Maximov, Anton ; Südhof, Thomas C. ; Bezprozvanny, Ilya. / Association of neuronal calcium channels with modular adaptor proteins. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 35. pp. 24453-24456.
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