TRPC6 channels and their binding partners in podocytes: role in glomerular filtration and pathophysiology.
Loss or dysfunction of podocytes is a major cause of glomerular kidney disease. Several genetic forms of glomerular disease are caused by mutations in genes that encode structural elements of the slit diaphragm or the underlying cytoskeleton of podocyte foot processes. The recent discovery that gain-of-function mutations in Ca(2+)-permeable canonical transient receptor potential-6 channels (TRPC6) underlie a subset of familial forms of focal segmental glomerulosclerosis (FSGS) has focused attention on the basic cellular physiology of podocytes. Several recent studies have examined the role of Ca(2+) dynamics in normal podocyte function and their possible contributions to glomerular disease. This review summarizes the properties of TRPC6 and related channels, focusing on their permeation and gating properties, the nature of mutations associated with familial FSGS, and the role of TRPC channels in podocyte cell biology as well as in glomerular pathophysiology. TRPC6 interacts with several proteins in podocytes, including essential slit diaphragm proteins and mechanosensitive large-conductance Ca(2+)-activated K(+) channels. The signaling dynamics controlling ion channel function and localization in podocytes appear to be quite complex.
Dryer
Stuart E
SE
Dept. of Biology and Biochemistry, Univ. of Houston, 4800 Calhoun, Houston, TX 77204-5001, USA. SDryer@uh.edu
Reiser
Jochen
J
D002118:Calcium / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D009154:Mutation / Q000235:genetics; D050199:Podocytes / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*; D000074287:TRPC6 Cation Channel
D024681:Potassium Channels, Calcium-Activated; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D002118:Calcium