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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/118106
Ver los metadatos del registro completo
id |
CONICETDig_7597531aaf754463f2754c050cdd4d29 |
---|---|
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 Técnicas2025-09-29T10:27:59Zoai: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:34982025-09-29 10:27:59.534CONICET 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 |
_version_ |
1844614282778509312 |
score |
13.070432 |