title: Dynamin Autonomously Regulates Podocyte Focal Adhesion Maturation.
abstract: Rho family GTPases, the prototypical members of which are Cdc42, Rac1, and RhoA, are molecular switches best known for regulating the actin cytoskeleton. In addition to the canonical small GTPases, the large GTPase dynamin has been implicated in regulating the actin cytoskeleton via direct dynamin-actin interactions. The physiologic role of dynamin in regulating the actin cytoskeleton has been linked to the maintenance of the kidney filtration barrier. Additionally, the small molecule Bis-T-23, which promotes actin-dependent dynamin oligomerization and thus, increases actin polymerization, improved renal health in diverse models of CKD, implicating dynamin as a potential therapeutic target for the treatment of CKD. Here, we show that treating cultured mouse podocytes with Bis-T-23 promoted stress fiber formation and focal adhesion maturation in a dynamin-dependent manner. Furthermore, Bis-T-23 induced the formation of focal adhesions and stress fibers in cells in which the RhoA signaling pathway was downregulated by multiple experimental approaches. Our study suggests that dynamin regulates focal adhesion maturation by a mechanism parallel to and synergistic with the RhoA signaling pathway. Identification of dynamin as one of the essential and autonomous regulators of focal adhesion maturation suggests a molecular mechanism that underlies the beneficial effect of Bis-T-23 on podocyte physiology.
authors.affiliation: Department of Medicine, Harvard Medical School, Division of Nephrology, Massachusetts General Hospital, Charlestown, Massachusetts; and Gu.Changkyu@mgh.harvard.edu ssever@mgh.harvard.edu.
authors.forename: Changkyu
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
authors.forename: Ha Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Medicine, Harvard Medical School, Division of Nephrology, Massachusetts General Hospital, Charlestown, Massachusetts; and.
authors.forename: Garrett
authors.initials: G
authors.lastname: Garborcauskas
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
authors.forename: Vineet
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Medicine, Harvard Medical School, Division of Nephrology, Massachusetts General Hospital, Charlestown, Massachusetts; and Gu.Changkyu@mgh.harvard.edu ssever@mgh.harvard.edu.
authors.forename: Sanja
authors.initials: S
authors.lastname: Sever
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D034281:Dynamins / Q000502:physiology*; D022001:Focal Adhesions / Q000502:physiology*; D051379:Mice; D050199:Podocytes / Q000502:physiology*; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D020742:rhoA GTP-Binding Protein; D034281:Dynamins
keywords: RhoA; actin; dynamin; podocyte