title: Calcium regulates podocyte actin dynamics.
abstract: Ca(2+)-mediated remodeling of the actin cytoskeleton is a dynamic process that regulates cell motility through the modulation of rho guanosine triphosphatase (GTPase) signaling. Kidney podocytes are unique, pericyte-like cells with a complex cellular organization consisting of a cell body, major processes, and foot processes (FPs). The FPs form a characteristic interdigitating pattern with FPs of neighboring podocytes, leaving in between filtration slits that are covered by the slit diaphragm (SD). The actin-based FP and the SD form the final barrier to proteinuria. Mutations affecting several podocyte proteins cause disruption of the filtration barrier and rearrangement of the highly dynamic podocyte actin cytoskeleton. Proteins regulating the plasticity of the podocyte actin cytoskeleton are therefore of critical importance for sustained kidney barrier function. Dynamic regulation of the actin-based contractile apparatus in podocyte FPs is essential for sustained kidney filter function. Thus, the podocyte represents an excellent model system to study calcium signaling and actin dynamics in a physiologic context. Here, we discuss the regulation of podocyte actin dynamics by angiotensin or bradykinin-mediated calcium influx and downstream Rho GTPase signaling pathways and how these pathways are operative in other cells including fibroblasts and cancer cells.
authors.affiliation: Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Charlestown, MA 02129, USA. greka.anna@mgh.harvard.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Greka
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000502:physiology; D008840:Microfilament Proteins / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D050778:NFATC Transcription Factors; C503968:Synpo protein, mouse; D050052:TRPC Cation Channels; D019703:Calcineurin; D020741:rho GTP-Binding Proteins; D002118:Calcium