TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

Jochen Reiser, Krishna R. Polu, Clemens C. Möller, Peter Kenlan, Mehmet M. Altintas, Changli Wei, Christian Faul, Stephanie Herbert, Ivan Villegas, Carmen Avila-Casado, Mary McGee, Hikaru Sugimoto, Dennis Brown, Raghu Kalluri, Peter Mundel, Paula L. Smith, David E. Clapham, Martin R. Pollak

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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.

Original languageEnglish (US)
Pages (from-to)739-744
Number of pages6
JournalNature genetics
Volume37
Issue number7
DOIs
StatePublished - Dec 15 2005

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ASJC Scopus subject areas

  • Genetics

Cite this

Reiser, J., Polu, K. R., Möller, C. C., Kenlan, P., Altintas, M. M., Wei, C., Faul, C., Herbert, S., Villegas, I., Avila-Casado, C., McGee, M., Sugimoto, H., Brown, D., Kalluri, R., Mundel, P., Smith, P. L., Clapham, D. E., & Pollak, M. R. (2005). TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nature genetics, 37(7), 739-744. https://doi.org/10.1038/ng1592