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

Low-voltage-activated T-type Ca(2+) 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...

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Autores principales: Cmarko, Leos, Stringer, Robin N., Jurkovicova-Tarabova, Bohumila, Vacik, Tomas, Lacinova, Lubica, Weiss, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721997/
https://www.ncbi.nlm.nih.gov/pubmed/34980194
http://dx.doi.org/10.1186/s13041-021-00891-7
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author Cmarko, Leos
Stringer, Robin N.
Jurkovicova-Tarabova, Bohumila
Vacik, Tomas
Lacinova, Lubica
Weiss, Norbert
author_facet Cmarko, Leos
Stringer, Robin N.
Jurkovicova-Tarabova, Bohumila
Vacik, Tomas
Lacinova, Lubica
Weiss, Norbert
author_sort Cmarko, Leos
collection PubMed
description Low-voltage-activated T-type Ca(2+) 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 Ca(v)3.2-interacting protein. In addition, we show that co-expression of SCAMP2 in mammalian cells expressing recombinant Ca(v)3.2 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 Ca(v)3.1 and Ca(v)3.3 channel isoforms. Finally, we show that SCAMP2-mediated knockdown of the T-type conductance is caused by the lack of Ca(v)3.2 expression at the cell surface as evidenced by the concomitant loss of intramembrane charge movement without decrease of total Ca(v)3.2 protein level. Taken together, our results indicate that SCAMP2 plays an important role in the trafficking of Ca(v)3.2 channels at the plasma membrane. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-021-00891-7.
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spelling pubmed-87219972022-01-06 Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels Cmarko, Leos Stringer, Robin N. Jurkovicova-Tarabova, Bohumila Vacik, Tomas Lacinova, Lubica Weiss, Norbert Mol Brain Micro Report Low-voltage-activated T-type Ca(2+) 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 Ca(v)3.2-interacting protein. In addition, we show that co-expression of SCAMP2 in mammalian cells expressing recombinant Ca(v)3.2 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 Ca(v)3.1 and Ca(v)3.3 channel isoforms. Finally, we show that SCAMP2-mediated knockdown of the T-type conductance is caused by the lack of Ca(v)3.2 expression at the cell surface as evidenced by the concomitant loss of intramembrane charge movement without decrease of total Ca(v)3.2 protein level. Taken together, our results indicate that SCAMP2 plays an important role in the trafficking of Ca(v)3.2 channels at the plasma membrane. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-021-00891-7. BioMed Central 2022-01-03 /pmc/articles/PMC8721997/ /pubmed/34980194 http://dx.doi.org/10.1186/s13041-021-00891-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Micro Report
Cmarko, Leos
Stringer, Robin N.
Jurkovicova-Tarabova, Bohumila
Vacik, Tomas
Lacinova, Lubica
Weiss, Norbert
Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
title Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
title_full Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
title_fullStr Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
title_full_unstemmed Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
title_short Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels
title_sort secretory carrier-associated membrane protein 2 (scamp2) regulates cell surface expression of t-type calcium channels
topic Micro Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721997/
https://www.ncbi.nlm.nih.gov/pubmed/34980194
http://dx.doi.org/10.1186/s13041-021-00891-7
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