Regulation of cofilin phosphorylation in glomerular podocytes by testis specific kinase 1 (TESK1).

Published online

Journal Article

Expression of a constitutively active Rho A (V14Rho) in podocytes in vivo induces albuminuria and foot process (FP) effacement. These effects may be mediated by the Rho A effector Rho kinase (ROK); but inhibition of ROK with Y27632 failed to attenuate albuminuria or FP effacement in V14Rho mice. ROK activates LIM kinases (LIMKs), which phosphorylate and inhibit the actin depolymerizing factor cofilin 1 (CFL1). Sustained phosphorylation of CFL1 is implicated in human nephrotic diseases, but Y27632 did not inhibit phosphorylation of CFL1 in vivo, despite effective ROK inhibition. CFL1 is also phosphorylated by testis-specific kinase 1 (TESK1) on the same serine residue. TESK1 was expressed in podocytes, and, similar to the in vivo situation, Y27632 had little effect on phospho-CFL1 (pCFL1) levels in cultured podocytes. In contrast, Y27632 reduced pCFL1 levels in TESK1 knockout (KO) cells. ROK inhibition enhanced podocyte motility but, the motility promoting effect of Y27632 was absent in TESK1 KO podocytes. Thus, TESK1 regulates podocyte cytoskeletal dynamics in glomerular podocytes and may play an important role in regulating glomerular filtration barrier integrity in glomerular disease processes.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Buckley, AF; Spurney, RF

Published Date

  • August 16, 2018

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 12286 -

PubMed ID

  • 30115939

Pubmed Central ID

  • 30115939

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-018-30115-3

Language

  • eng

Conference Location

  • England