title: Role of Rho-GTPases and their regulatory proteins in glomerular podocyte function.
abstract: Podocytes play a critical role in maintaining glomerular permselectivity. It has been long recognized that their intricate actin-based structures are tightly associated with their normal function; however, the precise mechanisms by which podocytes form and maintain their complex structure had been poorly understood until the intensive investigations on podocyte biology began in 1998, triggered by the breakthrough discovery of nephrin. This review summarizes the recent discoveries of the molecular mechanisms by which the actin cytoskeleton is regulated in podocytes. A particular focus will be on the role of the Rho-family of small GTPases, represented by RhoA, Rac1, and Cdc42. Rho-GTPases are known for their versatile cellular functions, most importantly for the actin regulatory roles. We will also discuss the potential roles of the 3 groups of proteins known to regulate Rho-GTPases, namely GTPase-activating proteins, guanine nucleotide exchange factors, and guanine nucleotide dissociation inhibitors.
authors.affiliation: Department of Medicine, McGill University Health Centre, Montreal, QC H3A 2B4, Canada.
authors.forename: Flaviana
authors.initials: F
authors.lastname: Mouawad
authors.forename: Harmony
authors.initials: H
authors.lastname: Tsui
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takano
mesh_terms: D008841:Actin Cytoskeleton / Q000201:enzymology; D000818:Animals; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005919:Glomerular Filtration Rate; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D023421:Models, Animal; D010539:Permeability; D050199:Podocytes / Q000201:enzymology*; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C113267:nephrin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein