A Ca v3.2/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 v3.2 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 v3.2 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 v3.2 channels in MPC9/3L-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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.