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Published on: January 10, 2011
Modulation of inactivation properties of CaV2.2 channels by 14-3-3 proteins
1Department of Neurobiology, Evelyn F. McKnight Brain Institute and Civitan International Research Center, School of Medicine, University of Alabama at Birmingham, 35294, USA.
Abstract:
Inactivation of presynaptic Ca(V)2.2 channels may play a role in regulating short-term synaptic plasticity. Here, we report a direct modulation of Ca(V)2.2 channel inactivation properties by 14-3-3, a family of signaling proteins involved in a wide range of biological processes. The structural elements critical for 14-3-3 binding and channel modulation lie in the carboxyl tail of the pore-forming alpha(1B) subunit, where we have identified two putative 14-3-3 interaction sites, including a phosphoserine-containing motif that directly binds to 14-3-3 and a second region near the EF hand and IQ domain. In transfected tsA 201 cells, 14-3-3 coexpression dramatically slows open-state inactivation and reduces cumulative inactivation of Ca(V)2.2 channels. In hippocampal neurons, interference with 14-3-3 binding accelerates Ca(V)2.2 channel inactivation and enhances short-term synaptic depression. These results demonstrate that 14-3-3 proteins are important regulators of Ca(V)2.2 channel activities and through this mechanism may contribute to their regulation of synaptic transmission and plasticity.
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