Sensitizing the Slit Diaphragm with TRPC6 ion channels.
Physiologic permeability of the glomerular capillary depends on the normal structure of podocyte foot processes forming a functioning slit diaphragm in between. Mutations in several podocyte genes as well as specific molecular pathways have been identified as the cause for progressive kidney failure with urinary protein loss. Podocyte injury is a hallmark of glomerular disease, which is generally displayed by the rearrangement of the podocyte slit diaphragm and the actin cytoskeleton. Recent studies demonstrate a unique role for the Ca(2+)-permeable ion channel protein TRPC6 as a regulator of glomerular ultrafiltration. In both genetic and acquired forms of proteinuric kidney disease, dysregulation of podocyte TRPC6 plays a pathogenic role. This article illustrates how recent findings add to emerging concepts in podocyte biology, particularly mechanosensation and signaling at the slit diaphragm.
Möller
Clemens C
CC
Department of Medicine, Program in Glomerular Disease and Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Flesche
Jan
J
Reiser
Jochen
J
D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000502:physiology* / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009404:Nephrotic Syndrome / Q000235:genetics; D050199:Podocytes / Q000502:physiology*; D011507:Proteinuria / Q000235:genetics; D051381:Rats; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000074287:TRPC6 Cation Channel
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C492146:Trpc6 protein, mouse