Role of γ-adducin in actin cytoskeleton rearrangements in podocyte pathophysiology

Wenjun Gao, Yedan Liu, Letao Fan, Baoying Zheng, Joshua R. Jefferson, Shaoxun Wang, Huawei Zhang, Xing Fang, Bond V. Nguyen, Tongyu Zhu, Richard J. Roman, Fan Fan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


We recently reported that the enhanced susceptibility to chronic kidney disease (CKD) in the fawn-hooded hypertensive (FHH) rat is caused, at least in part, by a mutation in γ-adducin (ADD3) that attenuates renal vascular function. The present study explored whether Add3 contributes to the modulation of podocyte structure and function using FHH and FHH.Add3 transgenic rats. The expression of ADD3 on the membrane of primary podocytes isolated from FHH was reduced compared with FHH. Add3 transgenic rats. We found that F-actin nets, which are typically localized in the lamellipodia, replaced unbranched stress fibers in conditionally immortalized mouse podocytes transfected with Add3 Dicer-substrate short interfering RNA (DsiRNA) and primary podocytes isolated from FHH rats. There were increased F/G-actin ratios and expression of the Arp2/3 complexes throughout FHH podocytes in association with reduced synaptopodin and RhoA but enhanced Rac1 and CDC42 expression in the renal cortex, glomeruli, and podocytes of FHH rats. The expression of nephrin at the slit diaphragm and the levels of focal adhesion proteins integrin-α3 and integrin-β1 were decreased in the glomeruli of FHH rats. Cell migration was enhanced and adhesion was reduced in podocytes of FHH rats as well as in immortalized mouse podocytes transfected with Add3 DsiRNA. Mean arterial pressures were similar in FHH and FHH.Add3 transgenic rats at 16 wk of age; however, FHH rats exhibited enhanced proteinuria associated with podocyte foot process effacement. These results demonstrate that reduced ADD3 function in FHH rats alters baseline podocyte pathophysiology by rearrangement of the actin cytoskeleton at the onset of proteinuria in young animals.

Original languageEnglish (US)
Pages (from-to)F97-F113
JournalAmerican Journal of Physiology - Renal Physiology
Issue number1
StatePublished - 2021
Externally publishedYes


  • Actin cytoskeleton
  • Glomerulus
  • Podocyte
  • Renal injury
  • γ-adducin

ASJC Scopus subject areas

  • Physiology
  • Urology


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