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How do T-type calcium channels control low-threshold exocytosis?

Abstract : Low-voltage-activated T-type calcium channels act as a major pathway for calcium entry near the resting membrane potential in a wide range of neuronal cell types. Several reports have uncovered an unrecognized feature of T-type channels in the control of vesicular neurotransmitter and hormone release, a process so far thought to be mediated exclusively by high-voltage-activated calcium channels. However, the underlying molecular mechanisms linking T-type calcium channels to vesicular exocytosis have remained enigmatic. In a recent study, we have reported that Ca(v)3.2 T-type channel forms a signaling complex with the neuronal Q-SNARE syntaxin-1A and SNAP-25. This interaction that relies on specific Ca(v)3.2 molecular determinants, not only modulates T-type channel activity, but was also found essential to support low-threshold exocytosis upon Ca(v)3.2 channel expression in MPC 9/3L-AH chromaffin cells. Overall, we have indentified an unrecognized regulation pathway of T-type calcium channels by SNARE proteins, and proposed the first molecular mechanism by which T-type channels could mediate low-threshold exocytosis.
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Submitted on : Thursday, November 29, 2012 - 5:05:06 PM
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Norbert Weiss, Gerald W. Zamponi, Michel de Waard. How do T-type calcium channels control low-threshold exocytosis?. Communicative and Integrative Biology, Taylor & Francis Open, 2012, 5 (4), pp.377-80. ⟨10.4161/cib.19997⟩. ⟨inserm-00759004⟩



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