Munc18: A presynaptic transmitter release site N type (CaV2.2) calcium channel interacting protein

Allen W. Chan, Rajesh Khanna, Qi Li, Elise F. Stanley

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Munc18 is a presynaptic protein that is essential for transmitter release. Recent studies have indicated that this protein is involved in secretory vesicle docking but its binding partners in this role remain a mystery. We demonstrate using the isolated calyx-type presynaptic terminal of the chick ciliary ganglion that staining for Munc18 colocalizes and covaries with that for transmitter release site N type calcium channels (CaV2.2), consistent with elements of a common release site complex. Biochemical analysis demonstrated that the protein coprecipitates with CaV2.2 from lysates of rat or chick brain, including its synaptic, long-splice variant; presynaptic terminal surface membrane proteins, and a cell line coexpressing Munc18 and CaV2.2. Munc18 bound with high affinity to the CaV2.2 II-III intracellular loop, low affinity to the I-II loop but not to other channel intracellular regions. Over-expression of Munc18 in dorsal root ganglion neurons did not affect CaV2.2 current amplitude or fast kinetics but siRNA-knockdown resulted in a negative shift in the steady state inactivation curve, an effect attributed to an indirect action via syntaxin 1. Recombinant Munc18 also coprecipitated strongly with the v-SNARE synaptotagmin, but only weakly with other SNAREs. Thus, the calcium channel may serve as a surface membrane platform anchoring a Munc18-containing bridge to synaptotagmin and the synaptic vesicle.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalChannels
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • CaV22
  • Calcium channel
  • DRG
  • Docking complex
  • Exocytosis
  • Munc18
  • N-type
  • Synprint
  • Unc18
  • Vesicle docking

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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