Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Poteser, M; Graziani, A; Rosker, C; Eder, P; Derler, I; Kahr, H; Zhu, MX; Romanin, C; Groschner, K.
TRPC3 and TRPC4 associate to form a redox-sensitive cation channel. Evidence for expression of native TRPC3-TRPC4 heteromeric channels in endothelial cells.
J Biol Chem. 2006; 281(19):13588-13595
Doi: 10.1074/jbc.M512205200
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Führende Autor*innen der Med Uni Graz
- Groschner Klaus
- Poteser Michael
- Co-Autor*innen der Med Uni Graz
- Rosker Christian
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Canonical transient receptor potential proteins (TRPC) have been proposed to form homo- or heteromeric cation channels in a variety of tissues, including the vascular endothelium. Assembly of TRPC multimers is incompletely understood. In particular, heteromeric assembly of distantly related TRPC isoforms is still a controversial issue. Because we have previously suggested TRPC proteins as the basis of the redox-activated cation conductance of porcine aortic endothelial cells (PAECs), we set out to analyze the TRPC subunit composition of endogenous endothelial TRPC channels and report here on a redox-sensitive TRPC3-TRPC4 channel complex. The ability of TRPC3 and TRPC4 proteins to associate and to form a cation-conducting pore complex was supported by four lines of evidence as follows: 1) Co-immunoprecipitation experiments in PAECs and in HEK293 cells demonstrated the association of TRPC3 and TRPC4 in the same complex. 2) Fluorescence resonance energy transfer analysis demonstrated TRPC3-TRPC4 association, involving close proximity between the N terminus of TRPC4 and the C terminus of TRPC3 subunits. 3) Co-expression of TRPC3 and TRPC4 in HEK293 cells generated a channel that displayed distinct biophysical and regulatory properties. 4) Expression of dominant-negative TRPC4 proteins suppressed TRPC3-related channel activity in the HEK293 expression system and in native endothelial cells. Specifically, an extracellularly hemagglutinin (HA)-tagged TRPC4 mutant, which is sensitive to blockage by anti-HA-antibody, was found to transfer anti-HA sensitivity to both TRPC3-related currents in the HEK293 expression system and the redox-sensitive cation conductance of PAECs. We propose TRPC3 and TRPC4 as subunits of native endothelial cation channels that are governed by the cellular redox state.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Line -
- Endothelial Cells - metabolism
- Gene Expression Regulation -
- Humans -
- Membrane Potentials -
- Mice -
- Oxidation-Reduction -
- Oxidative Stress -
- Protein Binding -
- Protein Structure, Quaternary -
- Swine -
- TRPC Cation Channels - chemistry TRPC Cation Channels - genetics TRPC Cation Channels - metabolism