title: Balancing calcium signals through TRPC5 and TRPC6 in podocytes.
abstract: Calcium (Ca(2+)) ions are important mediators of cellular homeostasis owing to their ability to elicit a dynamic, transient, and tightly regulated range of biochemical responses. More than a decade ago, a nonselective, Ca(2+)-permeable, cationic conductance was identified in podocytes downstream of angiotensin II (Ang II) signaling, but its molecular structure remained elusive. Six years ago, transient receptor potential canonical 6 (TRPC6) mutations were found in families with hereditary FSGS, and TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for this previously described, nonselective, cationic current in podocytes. Ang II activation engages this Ca(2+) influx to modulate the actin cytoskeleton in podocytes. These discoveries dovetail with previously described regulation of actin dynamics by the Ca(2+)-activated phosphatase, calcineurin, and the emergence of Rho GTPases as critical regulators of podocyte function in health and disease. Understanding the interconnected signaling regulated by Ca(2+) currents offers potential new therapeutic targets and highlights the notion that synergistic therapies targeting multiple levels of biochemistry may be useful in treating proteinuric kidney disease.
authors: Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. greka.anna@mgh.harvard.edu
authors: Anna
authors: A
authors: Greka
authors: Peter
authors: P
authors: Mundel
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D050199:Podocytes / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism*; D000074287:TRPC6 Cation Channel
chemical_list: D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human