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Kidney Week

Abstract: FR-PO368

α-Parvin, an Integrin-Related Scaffold Protein, Regulates Actin Turnover to Facilitate Kidney Ureteric Bud Development

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine


  • Dong, Xinyu, Vanderbilt University, Nashville, Tennessee, United States
  • Bock, Fabian, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Bulus, Nada M., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Viquez, Olga, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Pozzi, Ambra, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Zent, Roy, Vanderbilt University Medical Center, Nashville, Tennessee, United States

The kidney collecting duct develops by iterative branching of the ureteric bud (UB), a process that requires cell migration that is tightly regulated by actin dynamics. α-Parvin is a scaffold protein associated with integrins, the major extracellular matrix (ECM) receptors. Parvin controls actin dynamics by binding to the actin filaments and by regulating the activation of the Rho family of GTPases (Rho, Rac, and Cdc42), which restructure the actin cytoskeleton during key cell activities such as cell migration. The Rho GTPases function in part by depolymerizing filamentous actin (F-actin) via the ADF/cofilin proteins. We previously showed α-Parvin is critical for mouse kidney development because global α-Parvin knockout led to kidney agenesis. In this study, we defined the mechanism of how α-Parvin regulates UB branching.


We deleted α-Parvin at the initiation of UB development (E10.5) by crossing the α-Parvinfl/fl with a HOXB7Cre mice. To study the molecular function of α-Parvin, we generated α-Parvin-null collecting duct (CD) cells by deleting α-Parvin using adenoviral-mediated delivery of plasmids encoding Cre recombinase from isolated CDs of the α-Parvinfl/fl mice.


The α-Parvinfl/fl:HoxB7Cre mice were born with severely dysmorphic kidneys leading to death by 3 months. The kidneys showed a significant UB branching defect by E11.5. In addition to the decreased branching, the UB branches were abnormally shaped, with a larger tubular diameter and an increased number of cells around the circumference. There was excessive basal F-actin in the UB and prominent F-actin formation in α-Parvin-null CD cells, suggesting a loss of actin depolymerization. Mechanistically, the α-Parvin-null CD cells and kidneys had a profound increase in RhoA and Cdc42 activity. The major actin-depolymerizing factor downstream of the Rho GTPases, cofilin, was also inactivated in both the papilla of α-Parvin-null kidneys and CD cells. Consequently, the α-Parvin-null CD cells showed increased cell adhesion and spreading but impaired migration on ECM. Finally, inhibition of RhoA and Cdc42 was sufficient to reverse the inactivation of cofilin and rescue the α-Parvin-null phenotypes.


α-Parvin is required for UB development and it exerts its function by regulating the Rho/cofilin pathway that finetunes the actin dynamics.


  • NIDDK Support