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T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B Garcia-Caballero, Agustin; Zhang, Fang-Xiong; Hodgkinson, Victoria; Huang, Junting; Chen, Lina; Souza, Ivana A.; Cain, Stuart; Kass, Jennifer; Alles, Sascha; Snutch, Terrance P.; Zamponi, Gerald W.

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.

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Title
T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B
Creator
Garcia-Caballero, Agustin; Zhang, Fang-Xiong; Hodgkinson, Victoria; Huang, Junting; Chen, Lina; Souza, Ivana A.; Cain, Stuart; Kass, Jennifer; Alles, Sascha; Snutch, Terrance P.; Zamponi, Gerald W.
Contributor
Michael Smith Laboratories; Djavad Mowafaghian Centre for Brain Health
Publisher
BioMed Central
Date Issued
2018-05-02
Description
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.
Subject
T-type channels; Spectrin (α/β); Ankyrin B; Trafficking; Cav3.1; Cav3.2
Genre
Article
Type
Text
Language
eng
Date Available
2018-05-08
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0366217
URI
http://hdl.handle.net/2429/65792
Affiliation
Other UBC; Non UBC
Citation
Molecular Brain. 2018 May 02;11(1):24
Publisher DOI
10.1186/s13041-018-0368-5
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)