title: A Ca(v)3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis.
abstract: T-type calcium channels represent a key pathway for Ca(2+) entry near the resting membrane potential. Increasing evidence supports a unique role of these channels in fast and low-threshold exocytosis in an action potential-independent manner, but the underlying molecular mechanisms have remained unknown. Here, we report the existence of a syntaxin-1A/Ca(v)3.2 T-type calcium channel signaling complex that relies on molecular determinants that are distinct from the synaptic protein interaction site (synprint) found in synaptic high voltage-activated calcium channels. This interaction potently modulated Ca(v)3.2 channel activity, by reducing channel availability. Other members of the T-type calcium channel family were also regulated by syntaxin-1A, but to a smaller extent. Overexpression of Ca(v)3.2 channels in MPC 9/3L-AH chromaffin cells induced low-threshold secretion that could be prevented by uncoupling the channels from syntaxin-1A. Altogether, our findings provide compelling evidence for the existence of a syntaxin-1A/T-type Ca(2+) channel signaling complex and provide new insights into the molecular mechanism by which these channels control low-threshold exocytosis.
authors: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary T2N4N1, Canada.
authors: Norbert
authors: N
authors: Weiss
authors: Shahid
authors: S
authors: Hameed
authors: José M
authors: JM
authors: Fernández-Fernández
authors: Katell
authors: K
authors: Fablet
authors: Maria
authors: M
authors: Karmazinova
authors: Cathy
authors: C
authors: Poillot
authors: Juliane
authors: J
authors: Proft
authors: Lina
authors: L
authors: Chen
authors: Isabelle
authors: I
authors: Bidaud
authors: Arnaud
authors: A
authors: Monteil
authors: Sylvaine
authors: S
authors: Huc-Brandt
authors: Lubica
authors: L
authors: Lacinova
authors: Philippe
authors: P
authors: Lory
authors: Gerald W
authors: GW
authors: Zamponi
authors: Michel
authors: M
authors: De Waard
mesh_terms: D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D046912:Multiprotein Complexes; D050827:Syntaxin 1