Dynamin autonomously regulates podocyte focal adhesion maturation

Changkyu Gu, Ha Won Lee, Garrett Garborcauskas, Jochen Reiser, Vineet Gupta, Sanja Sever

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Rho familyGTPases, the prototypicalmembers of which are Cdc42, Rac1, and RhoA, aremolecular 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.

Original languageEnglish (US)
Pages (from-to)446-451
Number of pages6
JournalJournal of the American Society of Nephrology
Issue number2
StatePublished - Feb 2017
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


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