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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F23%3A43925832" target="_blank" >RIV/00216208:11120/23:43925832 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1080/19336950.2023.2230776" target="_blank" >https://doi.org/10.1080/19336950.2023.2230776</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/19336950.2023.2230776" target="_blank" >10.1080/19336950.2023.2230776</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson&apos;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.

Název v anglickém jazyce

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

Popis výsledku anglicky

Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson&apos;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Channels

ISSN

1933-6950

e-ISSN

1933-6969

Svazek periodika

17

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

2230776

Kód UT WoS článku

001016722500001

EID výsledku v databázi Scopus

2-s2.0-85164232677