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Cross talk between β subunits, intracellular Ca2+ signaling, and SNAREs in the modulation of CaV 2.1 channel steady-state inactivation

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dc.contributor.author Serra Pascual, Selma A., 1981-
dc.contributor.author Gené, Gemma
dc.contributor.author Elorza Vidal, Xabier
dc.contributor.author Fernández-Fernández, José Manuel, 1967-
dc.date.accessioned 2018-04-25T07:24:31Z
dc.date.available 2018-04-25T07:24:31Z
dc.date.issued 2018
dc.identifier.citation Serra SA, Gené GG, Elorza-Vidal X, Fernández-Fernández JM. Cross talk between beta subunits, intracellular Ca(2+) signaling, and SNAREs in the modulation of CaV 2.1 channel steady-state inactivation. Physiol Rep. 2018 Jan; 6(2): e13557. DOI: 10.14814/phy2.13557
dc.identifier.issn 2051-817X
dc.identifier.uri http://hdl.handle.net/10230/34445
dc.description.abstract Modulation of CaV 2.1 channel activity plays a key role in interneuronal communication and synaptic plasticity. SNAREs interact with a specific synprint site at the second intracellular loop (LII-III) of the CaV 2.1 pore-forming α1A subunit to optimize neurotransmitter release from presynaptic terminals by allowing secretory vesicles docking near the Ca2+ entry pathway, and by modulating the voltage dependence of channel steady-state inactivation. Ca2+ influx through CaV 2.1 also promotes channel inactivation. This process seems to involve Ca2+ -calmodulin interaction with two adjacent sites in the α1A carboxyl tail (C-tail) (the IQ-like motif and the Calmodulin-Binding Domain (CBD) site), and contributes to long-term potentiation and spatial learning and memory. Besides, binding of regulatory β subunits to the α interaction domain (AID) at the first intracellular loop (LI-II) of α1A determines the degree of channel inactivation by both voltage and Ca2+ . Here, we explore the cross talk between β subunits, Ca2+ , and syntaxin-1A-modulated CaV 2.1 inactivation, highlighting the α1A domains involved in such process. β3 -containing CaV 2.1 channels show syntaxin-1A-modulated but no Ca2+ -dependent steady-state inactivation. Conversely, β2a -containing CaV 2.1 channels show Ca2+ -dependent but not syntaxin-1A-modulated steady-state inactivation. A LI-II deletion confers Ca2+ -dependent inactivation and prevents modulation by syntaxin-1A in β3 -containing CaV 2.1 channels. Mutation of the IQ-like motif, unlike CBD deletion, abolishes Ca2+ -dependent inactivation and confers modulation by syntaxin-1A in β2a -containing CaV 2.1 channels. Altogether, these results suggest that LI-II structural modifications determine the regulation of CaV 2.1 steady-state inactivation either by Ca2+ or by SNAREs but not by both.
dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness (Grants SAF2012‐31089 and SAF2015‐69762‐R to JMF‐F, and Grant MDM‐2014‐0370 through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”), and FEDER Funds.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof Physiol Rep. 2018 Jan; 6(2): e13557
dc.rights © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Cross talk between β subunits, intracellular Ca2+ signaling, and SNAREs in the modulation of CaV 2.1 channel steady-state inactivation
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.14814/phy2.13557
dc.subject.keyword Ca2+-calmodulin
dc.subject.keyword CaV2.1 domains for SNARE-mediated modulation
dc.subject.keyword CaV2.1 steady-state inactivation
dc.subject.keyword CaVβ subunits
dc.subject.keyword Presynaptic voltage-gated CaV2.1 channels
dc.subject.keyword Syntaxin-1A
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012‐31089
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015‐69762‐R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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