LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells

Autores
Lingle, Christopher J.; Martinez Espinosa, Pedro L.; Yang Hood, Aizhen; Boero, Luis Ezequiel; Payne, Shelby; Persic, Dora; V-Ghaffari, Babak; Xiao, Maolei; Zhou, Yu; Xia, Xiao Ming; Pyott, Sonja J.; Rutherford, Mark A.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca2+- and voltage-activated large conductance Ca2+-activated K+ channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (−60 mV) even in the absence of intracellular Ca2+ elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca2+ channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat–containing (LRRC) regulatory γ subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs from Lrrc26 knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs from Lrrc52 KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK α subunits shifts BK current gating about −90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning.
Fil: Lingle, Christopher J.. Washington University in St. Louis; Estados Unidos
Fil: Martinez Espinosa, Pedro L.. Washington University in St. Louis; Estados Unidos
Fil: Yang Hood, Aizhen. Washington University in St. Louis; Estados Unidos
Fil: Boero, Luis Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Payne, Shelby. Washington University in St. Louis; Estados Unidos
Fil: Persic, Dora. University of Groningen; Países Bajos
Fil: V-Ghaffari, Babak. Washington University in St. Louis; Estados Unidos
Fil: Xiao, Maolei. Washington University in St. Louis; Estados Unidos
Fil: Zhou, Yu. Washington University in St. Louis; Estados Unidos
Fil: Xia, Xiao Ming. Washington University in St. Louis; Estados Unidos
Fil: Pyott, Sonja J.. University of Groningen; Países Bajos
Fil: Rutherford, Mark A.. Washington University in St. Louis; Estados Unidos
Materia
BK CHANNELS
AUXILIARY SUBUNITS
INNER HAIR CELLS
LRRC52
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/108308
Acceder
id CONICETDig_f47b4622d1a8d064d3f94f0a65744b5d
oai_identifier_str oai:ri.conicet.gov.ar:11336/108308
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cellsLingle, Christopher J.Martinez Espinosa, Pedro L.Yang Hood, AizhenBoero, Luis EzequielPayne, ShelbyPersic, DoraV-Ghaffari, BabakXiao, MaoleiZhou, YuXia, Xiao MingPyott, Sonja J.Rutherford, Mark A.BK CHANNELSAUXILIARY SUBUNITSINNER HAIR CELLSLRRC52https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca2+- and voltage-activated large conductance Ca2+-activated K+ channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (−60 mV) even in the absence of intracellular Ca2+ elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca2+ channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat–containing (LRRC) regulatory γ subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs from Lrrc26 knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs from Lrrc52 KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK α subunits shifts BK current gating about −90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning.Fil: Lingle, Christopher J.. Washington University in St. Louis; Estados UnidosFil: Martinez Espinosa, Pedro L.. Washington University in St. Louis; Estados UnidosFil: Yang Hood, Aizhen. Washington University in St. Louis; Estados UnidosFil: Boero, Luis Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Payne, Shelby. Washington University in St. Louis; Estados UnidosFil: Persic, Dora. University of Groningen; Países BajosFil: V-Ghaffari, Babak. Washington University in St. Louis; Estados UnidosFil: Xiao, Maolei. Washington University in St. Louis; Estados UnidosFil: Zhou, Yu. Washington University in St. Louis; Estados UnidosFil: Xia, Xiao Ming. Washington University in St. Louis; Estados UnidosFil: Pyott, Sonja J.. University of Groningen; Países BajosFil: Rutherford, Mark A.. Washington University in St. Louis; Estados UnidosNational Academy of Sciences2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/108308Lingle, Christopher J.; Martinez Espinosa, Pedro L.; Yang Hood, Aizhen; Boero, Luis Ezequiel; Payne, Shelby; et al.; LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 116; 37; 9-2019; 18397-184030027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/116/37/18397info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1907065116info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:24Zoai:ri.conicet.gov.ar:11336/108308instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:25.022CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
title LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
spellingShingle LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
Lingle, Christopher J.
BK CHANNELS
AUXILIARY SUBUNITS
INNER HAIR CELLS
LRRC52
title_short LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
title_full LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
title_fullStr LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
title_full_unstemmed LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
title_sort LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
dc.creator.none.fl_str_mv Lingle, Christopher J.
Martinez Espinosa, Pedro L.
Yang Hood, Aizhen
Boero, Luis Ezequiel
Payne, Shelby
Persic, Dora
V-Ghaffari, Babak
Xiao, Maolei
Zhou, Yu
Xia, Xiao Ming
Pyott, Sonja J.
Rutherford, Mark A.
author Lingle, Christopher J.
author_facet Lingle, Christopher J.
Martinez Espinosa, Pedro L.
Yang Hood, Aizhen
Boero, Luis Ezequiel
Payne, Shelby
Persic, Dora
V-Ghaffari, Babak
Xiao, Maolei
Zhou, Yu
Xia, Xiao Ming
Pyott, Sonja J.
Rutherford, Mark A.
author_role author
author2 Martinez Espinosa, Pedro L.
Yang Hood, Aizhen
Boero, Luis Ezequiel
Payne, Shelby
Persic, Dora
V-Ghaffari, Babak
Xiao, Maolei
Zhou, Yu
Xia, Xiao Ming
Pyott, Sonja J.
Rutherford, Mark A.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BK CHANNELS
AUXILIARY SUBUNITS
INNER HAIR CELLS
LRRC52
topic BK CHANNELS
AUXILIARY SUBUNITS
INNER HAIR CELLS
LRRC52
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca2+- and voltage-activated large conductance Ca2+-activated K+ channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (−60 mV) even in the absence of intracellular Ca2+ elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca2+ channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat–containing (LRRC) regulatory γ subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs from Lrrc26 knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs from Lrrc52 KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK α subunits shifts BK current gating about −90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning.
Fil: Lingle, Christopher J.. Washington University in St. Louis; Estados Unidos
Fil: Martinez Espinosa, Pedro L.. Washington University in St. Louis; Estados Unidos
Fil: Yang Hood, Aizhen. Washington University in St. Louis; Estados Unidos
Fil: Boero, Luis Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Payne, Shelby. Washington University in St. Louis; Estados Unidos
Fil: Persic, Dora. University of Groningen; Países Bajos
Fil: V-Ghaffari, Babak. Washington University in St. Louis; Estados Unidos
Fil: Xiao, Maolei. Washington University in St. Louis; Estados Unidos
Fil: Zhou, Yu. Washington University in St. Louis; Estados Unidos
Fil: Xia, Xiao Ming. Washington University in St. Louis; Estados Unidos
Fil: Pyott, Sonja J.. University of Groningen; Países Bajos
Fil: Rutherford, Mark A.. Washington University in St. Louis; Estados Unidos
description The perception of sound relies on sensory hair cells in the cochlea that convert the mechanical energy of sound into release of glutamate onto postsynaptic auditory nerve fibers. The hair cell receptor potential regulates the strength of synaptic transmission and is shaped by a variety of voltage-dependent conductances. Among these conductances, the Ca2+- and voltage-activated large conductance Ca2+-activated K+ channel (BK) current is prominent, and in mammalian inner hair cells (IHCs) displays unusual properties. First, BK currents activate at unprecedentedly negative membrane potentials (−60 mV) even in the absence of intracellular Ca2+ elevations. Second, BK channels are positioned in clusters away from the voltage-dependent Ca2+ channels that mediate glutamate release from IHCs. Here, we test the contributions of two recently identified leucine-rich-repeat–containing (LRRC) regulatory γ subunits, LRRC26 and LRRC52, to BK channel function and localization in mouse IHCs. Whereas BK currents and channel localization were unaltered in IHCs from Lrrc26 knockout (KO) mice, BK current activation was shifted more than +200 mV in IHCs from Lrrc52 KO mice. Furthermore, the absence of LRRC52 disrupted BK channel localization in the IHCs. Given that heterologous coexpression of LRRC52 with BK α subunits shifts BK current gating about −90 mV, to account for the profound change in BK activation range caused by removal of LRRC52, we suggest that additional factors may help define the IHC BK gating range. LRRC52, through stabilization of a macromolecular complex, may help retain some other components essential both for activation of BK currents at negative membrane potentials and for appropriate BK channel positioning.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/108308
Lingle, Christopher J.; Martinez Espinosa, Pedro L.; Yang Hood, Aizhen; Boero, Luis Ezequiel; Payne, Shelby; et al.; LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 116; 37; 9-2019; 18397-18403
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/108308
identifier_str_mv Lingle, Christopher J.; Martinez Espinosa, Pedro L.; Yang Hood, Aizhen; Boero, Luis Ezequiel; Payne, Shelby; et al.; LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 116; 37; 9-2019; 18397-18403
0027-8424
1091-6490
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/116/37/18397
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1907065116
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268664244469760
score 13.13397

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