The C-terminus of human Ca(v)2.3 voltage-gated calcium channel interacts with alternatively spliced calmodulin-2 expressed in two human cell lines.

Marcel A Kamp, Behzad Shakeri, Etienne E Tevoufouet, Andreas Krieger, Margit Henry, Kerstin Behnke, Stefan Herzig, Jürgen Hescheler, Kayalvizhi Radhakrishnan, Lucie Parent, Toni Schneider

Institute for Neurophysiology, University of Cologne, Germany.

Biochimica et biophysica acta 2012 Sep

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Ca(v)2.3 containing voltage-activated Ca(2+) channels are expressed in excitable cells and trigger neurotransmitter and peptide-hormone release. Their expression remote from the fast release sites leads to the accumulation of presynaptic Ca(2+) which can both, facilitate and inhibit the influx of Ca(2+) ions through Ca(v)2.3. The facilitated Ca(2+) influx was recently related to hippocampal postsynaptic facilitation and long term potentiation. To analyze Ca(2+) mediated modulation of cellular processes more in detail, protein partners of the carboxy terminal tail of Ca(v)2.3 were identified by yeast-2-hybrid screening, leading in two human cell lines to the detection of a novel, extended and rarely occurring splice variant of calmodulin-2 (CaM-2), called CaM-2-extended (CaM-2-ext). CaM-2-ext interacts biochemically with the C-terminus of Ca(v)2.3 similar to the classical CaM-2 as shown by co-immunoprecipitation. Functionally, only CaM-2-ext reduces whole cell inward currents significantly. The insertion of the novel 46 nts long exon and the consecutive expression of CaM-2-ext must be dependent on a new upstream translation initiation site which is only rarely used in the tested human cell lines. The structure of the N-terminal extension is predicted to be more hydrophobic than the remaining CaM-2-ext protein, suggesting that it may help to dock it to the lipophilic membrane surrounding. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Marcel A Kamp, Behzad Shakeri, Etienne E Tevoufouet, Andreas Krieger, Margit Henry, Kerstin Behnke, Stefan Herzig, Jürgen Hescheler, Kayalvizhi Radhakrishnan, Lucie Parent, Toni Schneider. The C-terminus of human Ca(v)2.3 voltage-gated calcium channel interacts with alternatively spliced calmodulin-2 expressed in two human cell lines. Biochimica et biophysica acta. 2012 Sep;1824(9):1045-57