Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels

Molecular Brain

Bohumila Jurkovicova-Tarabova¹  Lubica Lacinova¹  Tomas Vacik²  Leos Cmarko³  Norbert Weiss⁴  Robin N. Stringer⁵ 

[1]Center of Biosciences, Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia

[2]Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

[3]Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

[4]Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

[5]Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

[6]Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

[7]Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

[8]Center of Biosciences, Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia

[9]Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

[10]Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

关键词: Ion channels;    Calcium channels;    T-type channels;    Ca3.2 channels;    Secretory carrier-associated membrane protein 2;    SCAMP2;    Trafficking;   

DOI  :  10.1186/s13041-021-00891-7

来源: Springer

【 摘 要 】

Low-voltage-activated T-type Ca2+ channels are key regulators of neuronal excitability both in the central and peripheral nervous systems. Therefore, their recruitment at the plasma membrane is critical in determining firing activity patterns of nerve cells. In this study, we report the importance of secretory carrier-associated membrane proteins (SCAMPs) in the trafficking regulation of T-type channels. We identified SCAMP2 as a novel Cav3.2-interacting protein. In addition, we show that co-expression of SCAMP2 in mammalian cells expressing recombinant Cav3.2 channels caused an almost complete drop of the whole cell T-type current, an effect partly reversed by single amino acid mutations within the conserved cytoplasmic E peptide of SCAMP2. SCAMP2-induced downregulation of T-type currents was also observed in cells expressing Cav3.1 and Cav3.3 channel isoforms. Finally, we show that SCAMP2-mediated knockdown of the T-type conductance is caused by the lack of Cav3.2 expression at the cell surface as evidenced by the concomitant loss of intramembrane charge movement without decrease of total Cav3.2 protein level. Taken together, our results indicate that SCAMP2 plays an important role in the trafficking of Cav3.2 channels at the plasma membrane.

【 授权许可】

CC BY