title: Afadin regulates RhoA/Rho-associated protein kinase signaling to control formation of actin stress fibers in kidney podocytes.
abstract: The function of kidney podocytes is closely associated with actin cytoskeleton. Rho family small GTPase RhoA promotes stress fiber assembly through Rho-associated protein kinase (ROCK)-dependent myosin II phosphorylation and plays an important role in maintenance of actin stress fibers of podocytes. However, little is known how stress fiber assembly is regulated in podocytes. Here, we found that afadin, an actin filament-binding protein, is required for RhoA/ROCK-dependent formation of actin stress fibers in rat podocyte C7 cells. We show that depletion of afadin in C7 cells induced loss of actin stress fibers. Conversely, forced expression of afadin increased the formation of actin stress fibers. Depletion of afadin inactivated RhoA and reduced the phosphorylation of myosin II. Moreover, the DIL domain of afadin appears to be responsible for actin stress fiber formation. Thus, afadin mediates RhoA/ROCK signaling and contributes to the formation of actin stress fibers in podocyte cells.
authors.affiliation: Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, Kanagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shiino
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
authors.forename: Seisuke
authors.initials: S
authors.lastname: Hattori
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Ohta
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D005982:Glutathione Transferase / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology*; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D050199:Podocytes / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism*; D013696:Temperature; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; C507006:Afdn protein, rat; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D005982:Glutathione Transferase; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Rho family small GTPase; RhoA/ROCK; actin stress fiber; afadin; podocyte