I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.

The intracellular loops that interlink the four transmembrane domains of Ca(2+)- and Na(+)-channels (Ca(v), Na(v)) have critical roles in numerous forms of channel regulation. In particular, the intracellular loop that joins repeats I and II (I-II loop) in high voltage-activated (HVA) Ca(2+) channel...

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Autores principales:	Joel P Baumgart, Iuliia Vitko, Isabelle Bidaud, Artem Kondratskyi, Philippe Lory, Edward Perez-Reyes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a7c1bc0a7af04ff799dfaf61a90642da
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spelling	oai:doaj.org-article:a7c1bc0a7af04ff799dfaf61a90642da2021-11-25T06:11:10ZI-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.1932-620310.1371/journal.pone.0002976https://doaj.org/article/a7c1bc0a7af04ff799dfaf61a90642da2008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18714336/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The intracellular loops that interlink the four transmembrane domains of Ca(2+)- and Na(+)-channels (Ca(v), Na(v)) have critical roles in numerous forms of channel regulation. In particular, the intracellular loop that joins repeats I and II (I-II loop) in high voltage-activated (HVA) Ca(2+) channels possesses the binding site for Ca(v)beta subunits and plays significant roles in channel function, including trafficking the alpha(1) subunits of HVA channels to the plasma membrane and channel gating. Although there is considerable divergence in the primary sequence of the I-II loop of Ca(v)1/Ca(v)2 HVA channels and Ca(v)3 LVA/T-type channels, evidence for a regulatory role of the I-II loop in T-channel function has recently emerged for Ca(v)3.2 channels. In order to provide a comprehensive view of the role this intracellular region may play in the gating and surface expression in Ca(v)3 channels, we have performed a structure-function analysis of the I-II loop in Ca(v)3.1 and Ca(v)3.3 channels using selective deletion mutants. Here we show the first 60 amino acids of the loop (post IS6) are involved in Ca(v)3.1 and Ca(v)3.3 channel gating and kinetics, which establishes a conserved property of this locus for all Ca(v)3 channels. In contrast to findings in Ca(v)3.2, deletion of the central region of the I-II loop in Ca(v)3.1 and Ca(v)3.3 yielded a modest increase (+30%) and a reduction (-30%) in current density and surface expression, respectively. These experiments enrich our understanding of the structural determinants involved in Ca(v)3 function by highlighting the unique role played by the intracellular I-II loop in Ca(v)3.2 channel trafficking, and illustrating the prominent role of the gating brake in setting the slow and distinctive slow activation kinetics of Ca(v)3.3.Joel P BaumgartIuliia VitkoIsabelle BidaudArtem KondratskyiPhilippe LoryEdward Perez-ReyesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e2976 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joel P Baumgart Iuliia Vitko Isabelle Bidaud Artem Kondratskyi Philippe Lory Edward Perez-Reyes I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
description	The intracellular loops that interlink the four transmembrane domains of Ca(2+)- and Na(+)-channels (Ca(v), Na(v)) have critical roles in numerous forms of channel regulation. In particular, the intracellular loop that joins repeats I and II (I-II loop) in high voltage-activated (HVA) Ca(2+) channels possesses the binding site for Ca(v)beta subunits and plays significant roles in channel function, including trafficking the alpha(1) subunits of HVA channels to the plasma membrane and channel gating. Although there is considerable divergence in the primary sequence of the I-II loop of Ca(v)1/Ca(v)2 HVA channels and Ca(v)3 LVA/T-type channels, evidence for a regulatory role of the I-II loop in T-channel function has recently emerged for Ca(v)3.2 channels. In order to provide a comprehensive view of the role this intracellular region may play in the gating and surface expression in Ca(v)3 channels, we have performed a structure-function analysis of the I-II loop in Ca(v)3.1 and Ca(v)3.3 channels using selective deletion mutants. Here we show the first 60 amino acids of the loop (post IS6) are involved in Ca(v)3.1 and Ca(v)3.3 channel gating and kinetics, which establishes a conserved property of this locus for all Ca(v)3 channels. In contrast to findings in Ca(v)3.2, deletion of the central region of the I-II loop in Ca(v)3.1 and Ca(v)3.3 yielded a modest increase (+30%) and a reduction (-30%) in current density and surface expression, respectively. These experiments enrich our understanding of the structural determinants involved in Ca(v)3 function by highlighting the unique role played by the intracellular I-II loop in Ca(v)3.2 channel trafficking, and illustrating the prominent role of the gating brake in setting the slow and distinctive slow activation kinetics of Ca(v)3.3.
format	article
author	Joel P Baumgart Iuliia Vitko Isabelle Bidaud Artem Kondratskyi Philippe Lory Edward Perez-Reyes
author_facet	Joel P Baumgart Iuliia Vitko Isabelle Bidaud Artem Kondratskyi Philippe Lory Edward Perez-Reyes
author_sort	Joel P Baumgart
title	I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
title_short	I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
title_full	I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
title_fullStr	I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
title_full_unstemmed	I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
title_sort	i-ii loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/a7c1bc0a7af04ff799dfaf61a90642da
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I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels.

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