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 H 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

Research output: Contribution to journalArticle

568 Citations (Scopus)

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
Pages (from-to)739-744
Number of pages6
JournalNature Genetics
Volume37
Issue number7
DOIs
StatePublished - Dec 15 2005
Externally publishedYes

Fingerprint

Podocytes
Diaphragm
Kidney
Focal Segmental Glomerulosclerosis
Renal Insufficiency
Mutation
Ion Channels
Proteinuria
Genes
Permeability
Chromosomes
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Reiser, J., Polu, K. R., Möller, C. C., Kenlan, P., Altintas, M. M., Wei, C., ... 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

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. / Reiser, Jochen; Polu, Krishna R.; Möller, Clemens C.; Kenlan, Peter; Altintas, Mehmet M.; Wei, Changli; Faul, Christian H; Herbert, Stephanie; Villegas, Ivan; Avila-Casado, Carmen; McGee, Mary; Sugimoto, Hikaru; Brown, Dennis; Kalluri, Raghu; Mundel, Peter; Smith, Paula L.; Clapham, David E.; Pollak, Martin R.

In: Nature Genetics, Vol. 37, No. 7, 15.12.2005, p. 739-744.

Research output: Contribution to journalArticle

Reiser, J, Polu, KR, Möller, CC, Kenlan, P, Altintas, MM, Wei, C, Faul, CH, Herbert, S, Villegas, I, Avila-Casado, C, McGee, M, Sugimoto, H, Brown, D, Kalluri, R, Mundel, P, Smith, PL, Clapham, DE & Pollak, MR 2005, 'TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function', Nature Genetics, vol. 37, no. 7, pp. 739-744. https://doi.org/10.1038/ng1592
Reiser J, Polu KR, Möller CC, Kenlan P, Altintas MM, Wei C et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nature Genetics. 2005 Dec 15;37(7):739-744. https://doi.org/10.1038/ng1592
Reiser, Jochen ; Polu, Krishna R. ; Möller, Clemens C. ; Kenlan, Peter ; Altintas, Mehmet M. ; Wei, Changli ; Faul, Christian H ; Herbert, Stephanie ; Villegas, Ivan ; Avila-Casado, Carmen ; McGee, Mary ; Sugimoto, Hikaru ; Brown, Dennis ; Kalluri, Raghu ; Mundel, Peter ; Smith, Paula L. ; Clapham, David E. ; Pollak, Martin R. / TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. In: Nature Genetics. 2005 ; Vol. 37, No. 7. pp. 739-744.
@article{eed6afe0594d49bdad5257ae60fc822f,
title = "TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function",
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.",
author = "Jochen Reiser and Polu, {Krishna R.} and M{\"o}ller, {Clemens C.} and Peter Kenlan and Altintas, {Mehmet M.} and Changli Wei and Faul, {Christian H} and Stephanie Herbert and Ivan Villegas and Carmen Avila-Casado and Mary McGee and Hikaru Sugimoto and Dennis Brown and Raghu Kalluri and Peter Mundel and Smith, {Paula L.} and Clapham, {David E.} and Pollak, {Martin R.}",
year = "2005",
month = "12",
day = "15",
doi = "10.1038/ng1592",
language = "English",
volume = "37",
pages = "739--744",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

AU - Reiser, Jochen

AU - Polu, Krishna R.

AU - Möller, Clemens C.

AU - Kenlan, Peter

AU - Altintas, Mehmet M.

AU - Wei, Changli

AU - Faul, Christian H

AU - Herbert, Stephanie

AU - Villegas, Ivan

AU - Avila-Casado, Carmen

AU - McGee, Mary

AU - Sugimoto, Hikaru

AU - Brown, Dennis

AU - Kalluri, Raghu

AU - Mundel, Peter

AU - Smith, Paula L.

AU - Clapham, David E.

AU - Pollak, Martin R.

PY - 2005/12/15

Y1 - 2005/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=22844436647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22844436647&partnerID=8YFLogxK

U2 - 10.1038/ng1592

DO - 10.1038/ng1592

M3 - Article

C2 - 15924139

AN - SCOPUS:22844436647

VL - 37

SP - 739

EP - 744

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -