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Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels

Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson’s disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expres...

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Autores principales: Mustafá, Emilio R., Weiß, Konstantin, Weiss, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316736/
https://www.ncbi.nlm.nih.gov/pubmed/37389974
http://dx.doi.org/10.1080/19336950.2023.2230776
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author Mustafá, Emilio R.
Weiß, Konstantin
Weiss, Norbert
author_facet Mustafá, Emilio R.
Weiß, Konstantin
Weiss, Norbert
author_sort Mustafá, Emilio R.
collection PubMed
description Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson’s disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expression in the plasma membrane. Here, we show that similar to SCAMP2, the co-expression of SCAMP5 in tsA-201 cells expressing recombinant Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3 channels nearly abolished whole-cell T-type currents. Recording of intramembrane charge movements revealed that SCAMP5-induced inhibition of T-type currents is primarily caused by the reduced expression of functional channels in the plasma membrane. Moreover, we show that SCAMP5-mediated downregulation of Ca(v)3.2 channels is essentially preserved with disease-causing SCAMP5 R91W and G180W mutations. Hence, this study extends our previous findings with SCAMP2 and indicates that SCAMP5 also contributes to repressing the expression of T-type channels in the plasma membrane.
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spelling pubmed-103167362023-07-04 Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels Mustafá, Emilio R. Weiß, Konstantin Weiss, Norbert Channels (Austin) Brief Report Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson’s disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expression in the plasma membrane. Here, we show that similar to SCAMP2, the co-expression of SCAMP5 in tsA-201 cells expressing recombinant Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3 channels nearly abolished whole-cell T-type currents. Recording of intramembrane charge movements revealed that SCAMP5-induced inhibition of T-type currents is primarily caused by the reduced expression of functional channels in the plasma membrane. Moreover, we show that SCAMP5-mediated downregulation of Ca(v)3.2 channels is essentially preserved with disease-causing SCAMP5 R91W and G180W mutations. Hence, this study extends our previous findings with SCAMP2 and indicates that SCAMP5 also contributes to repressing the expression of T-type channels in the plasma membrane. Taylor & Francis 2023-06-30 /pmc/articles/PMC10316736/ /pubmed/37389974 http://dx.doi.org/10.1080/19336950.2023.2230776 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Brief Report
Mustafá, Emilio R.
Weiß, Konstantin
Weiss, Norbert
Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels
title Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels
title_full Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels
title_fullStr Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels
title_full_unstemmed Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels
title_short Secretory carrier-associated membrane protein 5 regulates cell-surface targeting of T-type calcium channels
title_sort secretory carrier-associated membrane protein 5 regulates cell-surface targeting of t-type calcium channels
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316736/
https://www.ncbi.nlm.nih.gov/pubmed/37389974
http://dx.doi.org/10.1080/19336950.2023.2230776
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