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

0551615 - ÚOCHB 2023 RIV GB eng J - Journal Article
Cmarko, Leoš - Stringer, Robin Nicholas - Jurkovicova-Tarabova, B. - Vacík, T. - Lacinová, L. - Weiss, Norbert
Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels.
Molecular Brain. Roč. 15, č. 1 (2022), č. článku 1. E-ISSN 1756-6606
Institutional support: RVO:61388963
Keywords : ion channels * calcium channels * T-type channels * Cav3.2 channels * secretory carrier-associated membrane protein 2 * SCAMP2 * trafficking
OECD category: Biochemistry and molecular biology
Impact factor: 3.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1186/s13041-021-00891-7

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.
Permanent Link: http://hdl.handle.net/11104/0326859