The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5

Onur K. Polat, Elena Isaeva, Yashwanth R. Sudhini, Brenna Knott, Ke Zhu, Manuel Noben, Varsha Suresh Kumar, Nicole Endlich, Steve Mangos, Tejasree Vallapu Reddy, Beata Samelko, Changli Wei, Mehmet M. Altintas, Stuart E. Dryer, Sanja Sever, Alexander Staruschenko, Jochen Reiser

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane. Other studies using TRPC5 gain-of-function transgenic mice have questioned the pathogenic role of TRPC5 in podocytes. Here, we show that TRPC5 over-expression or inhibition does not ameliorate proteinuria induced by the expression of constitutively active Rac1 in podocytes. Additionally, single-cell patch-clamp studies did not detect functional TRPC5 channels in primary cultures of podocytes. Thus, we conclude that TRPC5 plays a role redundant to that of TRPC6 in podocytes and is unlikely to be a useful therapeutic target for podocytopathies.

Original languageEnglish (US)
Pages (from-to)1056-1062
Number of pages7
JournalKidney International
Volume103
Issue number6
DOIs
StatePublished - Jun 2023
Externally publishedYes

Keywords

  • Rac1
  • TRPC5
  • calcium
  • focal segmental glomerulosclerosis

ASJC Scopus subject areas

  • Nephrology

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