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CACHD1 is an α2δ-like protein that modulates CaV3 voltage-gated calcium channel activity

Cottrell, G. S., Soubrane, C. H., Hounshell, J. A., Lin, H., Owenson, V., Rigby, M., Cox, P. J., Barker, B. S., Ottolini, M., Ince, S., Bauer, C. C., Perez-Reyes, E., Patel, M. K., Stevens, E. B. and Stephens, G. J. (2018) CACHD1 is an α2δ-like protein that modulates CaV3 voltage-gated calcium channel activity. The Journal of Neuroscience, 38 (4). pp. 9186-9201. ISSN 1529-2401

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To link to this item DOI: 10.1523/JNEUROSCI.3572-15.2018

Abstract/Summary

The putative cache (Ca2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the alpha2delta voltage-gated Ca2+ channel (VGCC) auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus and cerebellum, with a broadly similar tissue distribution to CaV3 subunits, in particular, CaV3.1. In expression studies, CACHD1 increased cell-surface localization of CaV3.1 and these proteins were in close proximity at the cell surface consistent with the formation of CACHD1-CaV3.1 complexes. In functional electrophysiological studies, co-expression of human CACHD1 with CaV3.1, CaV3.2 and CaV3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, alpha2delta-1 had no effect on peak current density or maximal conductance in either CaV3.1, CaV3.2 or CaV3.3. Comparison of CACHD1-mediated increases in CaV3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female E19 rats, CACHD1 overexpression increased CaV3-mediated action potential (AP) firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an alpha2delta-like protein that functionally modulates CaV3 voltage-gated calcium channel activity.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Centre for Integrative Neuroscience and Neurodynamics (CINN)
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:79082
Publisher:The Society for Neuroscience

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