The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1

Autores
Zhang, Peng; Luo, Ying; Chasan, Bernard; González Perrett, Silvia; Montalbetti, Nicolas; Timpanaro, Gustavo A.; Cantero, Maria del Rocio; Ramos, Arnolt J.; Goldmann, Wolfgang H.; Zhou, Jing; Cantiello, Horacio Fabio
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Polycystin-2 (PC2, TRPP2), the gene product of PKD2, whose mutations cause autosomal dominant polycystic kidney disease (ADPKD), belongs to the superfamily of TRP channels. PC2 is a non-selective cation channel, with multiple subconductance states. In this report, we explored structural and functional properties of PC2 and whether the conductance substates represent monomeric contributions to the channel complex. A kinetic analysis of spontaneous channel currents of PC2 showed that four intrinsic, non-stochastic subconductance states, which followed a staircase behavior, were both pH- and voltage-dependent. To confirm the oligomeric contributions to PC2 channel function, heteromeric PC2/TRPC1 channel complexes were also functionally assessed by single channel current analysis. Low pH inhibited the PC2 currents in PC2 homomeric complexes, but failed to affect PC2 currents in PC2/TRPC1 heteromeric complexes. Amiloride, in contrast, abolished PC2 currents in both the homomeric PC2 complexes and the heteromeric PC2/TRPC1 complexes, thus PC2/TRPC1 complexes have distinct functional properties from the homomeric complexes. The topological features of the homomeric PC2-, TRPC1- and heteromeric PC2/TRPC1 channel complexes, assessed by atomic force microscopy, were consistent with structural tetramers. TRPC1 homomeric channels had different average diameter and protruding height when compared with the PC2 homomers. The contribution of individual monomers to the PC2/TRPC1 hetero-complexes was easily distinguishable. The data support tetrameric models of both the PC2 and TRPC1 channels, where the overall conductance of a particular channel will depend on the contribution of the various functional monomers in the complex.
Fil: Zhang, Peng. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos
Fil: Luo, Ying. Brigham And Women's Hospital; Estados Unidos
Fil: Chasan, Bernard. Boston University; Estados Unidos
Fil: González Perrett, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Montalbetti, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Timpanaro, Gustavo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Cantero, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Ramos, Arnolt J.. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos
Fil: Goldmann, Wolfgang H.. Harvard Medical School; Estados Unidos. Universitat Erlangen-Nuremberg; Alemania. Massachusetts General Hospital; Estados Unidos
Fil: Zhou, Jing. Brigham And Women's Hospital; Estados Unidos
Fil: Cantiello, Horacio Fabio. Massachusetts General Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Harvard Medical School; Estados Unidos
Materia
PC2
Amiloride
Cations
Genes
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:11336/118106
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/118106
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1Zhang, PengLuo, YingChasan, BernardGonzález Perrett, SilviaMontalbetti, NicolasTimpanaro, Gustavo A.Cantero, Maria del RocioRamos, Arnolt J.Goldmann, Wolfgang H.Zhou, JingCantiello, Horacio FabioPC2AmilorideCationsGeneshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Polycystin-2 (PC2, TRPP2), the gene product of PKD2, whose mutations cause autosomal dominant polycystic kidney disease (ADPKD), belongs to the superfamily of TRP channels. PC2 is a non-selective cation channel, with multiple subconductance states. In this report, we explored structural and functional properties of PC2 and whether the conductance substates represent monomeric contributions to the channel complex. A kinetic analysis of spontaneous channel currents of PC2 showed that four intrinsic, non-stochastic subconductance states, which followed a staircase behavior, were both pH- and voltage-dependent. To confirm the oligomeric contributions to PC2 channel function, heteromeric PC2/TRPC1 channel complexes were also functionally assessed by single channel current analysis. Low pH inhibited the PC2 currents in PC2 homomeric complexes, but failed to affect PC2 currents in PC2/TRPC1 heteromeric complexes. Amiloride, in contrast, abolished PC2 currents in both the homomeric PC2 complexes and the heteromeric PC2/TRPC1 complexes, thus PC2/TRPC1 complexes have distinct functional properties from the homomeric complexes. The topological features of the homomeric PC2-, TRPC1- and heteromeric PC2/TRPC1 channel complexes, assessed by atomic force microscopy, were consistent with structural tetramers. TRPC1 homomeric channels had different average diameter and protruding height when compared with the PC2 homomers. The contribution of individual monomers to the PC2/TRPC1 hetero-complexes was easily distinguishable. The data support tetrameric models of both the PC2 and TRPC1 channels, where the overall conductance of a particular channel will depend on the contribution of the various functional monomers in the complex.Fil: Zhang, Peng. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados UnidosFil: Luo, Ying. Brigham And Women's Hospital; Estados UnidosFil: Chasan, Bernard. Boston University; Estados UnidosFil: González Perrett, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Montalbetti, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Timpanaro, Gustavo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Cantero, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ramos, Arnolt J.. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados UnidosFil: Goldmann, Wolfgang H.. Harvard Medical School; Estados Unidos. Universitat Erlangen-Nuremberg; Alemania. Massachusetts General Hospital; Estados UnidosFil: Zhou, Jing. Brigham And Women's Hospital; Estados UnidosFil: Cantiello, Horacio Fabio. Massachusetts General Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Harvard Medical School; Estados UnidosOxford University Press2009-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/118106Zhang, Peng; Luo, Ying; Chasan, Bernard; González Perrett, Silvia; Montalbetti, Nicolas; et al.; The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1; Oxford University Press; Human Molecular Genetics; 18; 7; 4-2009; 1238-12510964-6906CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/hmg/article/18/7/1238/673790info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722194/info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddp024info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:00:22Zoai:ri.conicet.gov.ar:11336/118106instacron: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:34982025-10-22 12:00:22.945CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
title The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
spellingShingle The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
Zhang, Peng
PC2
Amiloride
Cations
Genes
title_short The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
title_full The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
title_fullStr The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
title_full_unstemmed The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
title_sort The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1
dc.creator.none.fl_str_mv Zhang, Peng
Luo, Ying
Chasan, Bernard
González Perrett, Silvia
Montalbetti, Nicolas
Timpanaro, Gustavo A.
Cantero, Maria del Rocio
Ramos, Arnolt J.
Goldmann, Wolfgang H.
Zhou, Jing
Cantiello, Horacio Fabio
author Zhang, Peng
author_facet Zhang, Peng
Luo, Ying
Chasan, Bernard
González Perrett, Silvia
Montalbetti, Nicolas
Timpanaro, Gustavo A.
Cantero, Maria del Rocio
Ramos, Arnolt J.
Goldmann, Wolfgang H.
Zhou, Jing
Cantiello, Horacio Fabio
author_role author
author2 Luo, Ying
Chasan, Bernard
González Perrett, Silvia
Montalbetti, Nicolas
Timpanaro, Gustavo A.
Cantero, Maria del Rocio
Ramos, Arnolt J.
Goldmann, Wolfgang H.
Zhou, Jing
Cantiello, Horacio Fabio
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PC2
Amiloride
Cations
Genes
topic PC2
Amiloride
Cations
Genes
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Polycystin-2 (PC2, TRPP2), the gene product of PKD2, whose mutations cause autosomal dominant polycystic kidney disease (ADPKD), belongs to the superfamily of TRP channels. PC2 is a non-selective cation channel, with multiple subconductance states. In this report, we explored structural and functional properties of PC2 and whether the conductance substates represent monomeric contributions to the channel complex. A kinetic analysis of spontaneous channel currents of PC2 showed that four intrinsic, non-stochastic subconductance states, which followed a staircase behavior, were both pH- and voltage-dependent. To confirm the oligomeric contributions to PC2 channel function, heteromeric PC2/TRPC1 channel complexes were also functionally assessed by single channel current analysis. Low pH inhibited the PC2 currents in PC2 homomeric complexes, but failed to affect PC2 currents in PC2/TRPC1 heteromeric complexes. Amiloride, in contrast, abolished PC2 currents in both the homomeric PC2 complexes and the heteromeric PC2/TRPC1 complexes, thus PC2/TRPC1 complexes have distinct functional properties from the homomeric complexes. The topological features of the homomeric PC2-, TRPC1- and heteromeric PC2/TRPC1 channel complexes, assessed by atomic force microscopy, were consistent with structural tetramers. TRPC1 homomeric channels had different average diameter and protruding height when compared with the PC2 homomers. The contribution of individual monomers to the PC2/TRPC1 hetero-complexes was easily distinguishable. The data support tetrameric models of both the PC2 and TRPC1 channels, where the overall conductance of a particular channel will depend on the contribution of the various functional monomers in the complex.
Fil: Zhang, Peng. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos
Fil: Luo, Ying. Brigham And Women's Hospital; Estados Unidos
Fil: Chasan, Bernard. Boston University; Estados Unidos
Fil: González Perrett, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Montalbetti, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Timpanaro, Gustavo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Cantero, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Ramos, Arnolt J.. Harvard Medical School; Estados Unidos. Massachusetts General Hospital; Estados Unidos
Fil: Goldmann, Wolfgang H.. Harvard Medical School; Estados Unidos. Universitat Erlangen-Nuremberg; Alemania. Massachusetts General Hospital; Estados Unidos
Fil: Zhou, Jing. Brigham And Women's Hospital; Estados Unidos
Fil: Cantiello, Horacio Fabio. Massachusetts General Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Harvard Medical School; Estados Unidos
description Polycystin-2 (PC2, TRPP2), the gene product of PKD2, whose mutations cause autosomal dominant polycystic kidney disease (ADPKD), belongs to the superfamily of TRP channels. PC2 is a non-selective cation channel, with multiple subconductance states. In this report, we explored structural and functional properties of PC2 and whether the conductance substates represent monomeric contributions to the channel complex. A kinetic analysis of spontaneous channel currents of PC2 showed that four intrinsic, non-stochastic subconductance states, which followed a staircase behavior, were both pH- and voltage-dependent. To confirm the oligomeric contributions to PC2 channel function, heteromeric PC2/TRPC1 channel complexes were also functionally assessed by single channel current analysis. Low pH inhibited the PC2 currents in PC2 homomeric complexes, but failed to affect PC2 currents in PC2/TRPC1 heteromeric complexes. Amiloride, in contrast, abolished PC2 currents in both the homomeric PC2 complexes and the heteromeric PC2/TRPC1 complexes, thus PC2/TRPC1 complexes have distinct functional properties from the homomeric complexes. The topological features of the homomeric PC2-, TRPC1- and heteromeric PC2/TRPC1 channel complexes, assessed by atomic force microscopy, were consistent with structural tetramers. TRPC1 homomeric channels had different average diameter and protruding height when compared with the PC2 homomers. The contribution of individual monomers to the PC2/TRPC1 hetero-complexes was easily distinguishable. The data support tetrameric models of both the PC2 and TRPC1 channels, where the overall conductance of a particular channel will depend on the contribution of the various functional monomers in the complex.
publishDate 2009
dc.date.none.fl_str_mv 2009-04
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/11336/118106
Zhang, Peng; Luo, Ying; Chasan, Bernard; González Perrett, Silvia; Montalbetti, Nicolas; et al.; The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1; Oxford University Press; Human Molecular Genetics; 18; 7; 4-2009; 1238-1251
0964-6906
CONICET Digital
CONICET
url http://hdl.handle.net/11336/118106
identifier_str_mv Zhang, Peng; Luo, Ying; Chasan, Bernard; González Perrett, Silvia; Montalbetti, Nicolas; et al.; The multimeric structure of polycystin-2 (TRPP2): Structural - Functional correlates of homo- and hetero-multimers with TRPC1; Oxford University Press; Human Molecular Genetics; 18; 7; 4-2009; 1238-1251
0964-6906
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://academic.oup.com/hmg/article/18/7/1238/673790
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722194/
info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddp024
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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
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