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Letter
Nature Genetics  37, 739 - 744 (2005)
Published online: 27 May 2005; | doi:10.1038/ng1592

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

Jochen Reiser1, Krishna R Polu2, Clemens C Möller1, Peter Kenlan2, Mehmet M Altintas1, Changli Wei1, Christian Faul3, Stephanie Herbert2, Ivan Villegas4, Carmen Avila-Casado5, Mary McGee6, Hikaru Sugimoto7, Dennis Brown6, Raghu Kalluri7, Peter Mundel3, Paula L Smith8, David E Clapham8 & Martin R Pollak2

1  Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.

2  Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 USA.

3  Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029 USA.

4  Renal Unit, Instituto del Riñon-Fresenius Medical Care, Colombia.

5  Department of Pathology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico D.F. 14080, Mexico.

6  Program in Membrane Biology and Renal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.

7  Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.

8  Howard Hughes Medical Institute, Children's Hospital, Department of Cardiology, Boston, Massachusetts 02115, USA.

Correspondence should be addressed to Jochen Reiser jreiser@partners.org or Martin R Pollak mpollak@rics.bwh.harvard.edu
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.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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