The multimeric structure of polycystin-2 (TRPP2): structural–functional correlates of homo- and hetero-multimers with TRPC1
| Autor: | Arnolt J. Ramos, Peng Zhang, Bernard Chasan, Silvia González-Perrett, Nicolás Montalbetti, Ying Luo, Gustavo A. Timpanaro, Jing Zhou, Wolfgang H. Goldmann, Horacio F. Cantiello, María del Rocío Cantero |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
TRPP Cation Channels
Plasma protein binding Biology Microscopy Atomic Force Cell Line Amiloride Ciencias Biológicas TRPC1 Transient receptor potential channel Structure-Activity Relationship PC2 Cations Genetics medicine Homomeric Humans education Molecular Biology Genetics (clinical) TRPC Cation Channels education.field_of_study Conductance General Medicine Articles Hydrogen-Ion Concentration Biofísica Polycystin 2 Genes Biochemistry Biophysics Protein Multimerization Ion Channel Gating CIENCIAS NATURALES Y EXACTAS medicine.drug Protein Binding |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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