TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function
Open Access
- 27 May 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 37 (7), 739-744
- https://doi.org/10.1038/ng1592
Abstract
Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.Keywords
This publication has 27 references indexed in Scilit:
- Regulation of TRPC6 Channel Activity by Tyrosine PhosphorylationOnline Journal of Public Health Informatics, 2004
- Expression and relative abundance of short transient receptor potential channels in the rat renal microcirculationAmerican Journal of Physiology-Renal Physiology, 2004
- TRP channels as cellular sensorsNature, 2003
- Nephrin and CD2AP Associate with Phosphoinositide 3-OH Kinase and Stimulate AKT-Dependent SignalingMolecular and Cellular Biology, 2003
- Inherited PodocytopathiesJournal of the American Society of Nephrology, 2002
- Determinants of Vascular Permeability in the Kidney GlomerulusOnline Journal of Public Health Informatics, 2002
- Podocyte electrophysiology, in vivo and in vitroMicroscopy Research and Technique, 2002
- T-coffee: a novel method for fast and accurate multiple sequence alignmentJournal of Molecular Biology, 2000
- Positionally Cloned Gene for a Novel Glomerular Protein—Nephrin—Is Mutated in Congenital Nephrotic SyndromeMolecular Cell, 1998
- Synaptopodin: An Actin-associated Protein in Telencephalic Dendrites and Renal PodocytesThe Journal of cell biology, 1997