T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B

Molecular Brain

Ivana A. Souza¹  Junting Huang¹  Agustin Garcia-Caballero¹  Fang-Xiong Zhang¹  Gerald W. Zamponi¹  Victoria Hodgkinson¹  Lina Chen¹  Stuart Cain²  Terrance P. Snutch²  Jennifer Kass²  Sascha Alles² 

[1] Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary;Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British Colombia;

关键词: T-type channels;    Spectrin (α/β);    Ankyrin B;    Trafficking;    Cav3.1;    Cav3.2;   

DOI  :  10.1186/s13041-018-0368-5

来源: DOAJ

【 摘 要 】

Abstract This study describes the functional interaction between the Cav3.1 and Cav3.2 T-type calcium channels and cytoskeletal spectrin (α/β) and ankyrin B proteins. The interactions were identified utilizing a proteomic approach to identify proteins that interact with a conserved negatively charged cytosolic region present in the carboxy-terminus of T-type calcium channels. Deletion of this stretch of amino acids decreased binding of Cav3.1 and Cav3.2 calcium channels to spectrin (α/β) and ankyrin B and notably also reduced T-type whole cell current densities in expression systems. Furthermore, fluorescence recovery after photobleaching analysis of mutant channels lacking the proximal C-terminus region revealed reduced recovery of both Cav3.1 and Cav3.2 mutant channels in hippocampal neurons. Knockdown of spectrin α and ankyrin B decreased the density of endogenous Cav3.2 in hippocampal neurons. These findings reveal spectrin (α/β) / ankyrin B cytoskeletal and signaling proteins as key regulators of T-type calcium channels expressed in the nervous system.

【 授权许可】

Unknown