Modulation of inactivation properties of CaV2.2 channels by 14-3-3 proteins.
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.
Li
Yong
Y
Department of Neurobiology, Evelyn F. McKnight Brain Institute and Civitan International Research Center, School of Medicine, University of Alabama at Birmingham, 35294, USA.
Wu
Yuying
Y
Zhou
Yi
Y
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
D048948:14-3-3 Proteins; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; C419385:L-type calcium channel alpha(1C); D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase