The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5. Kidney Int 2023 Jun;103(6):1056-1062
Date
02/08/2023Pubmed ID
36750145Pubmed Central ID
PMC10200725DOI
10.1016/j.kint.2023.01.016Scopus ID
2-s2.0-85148731140 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
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.
Author List
Polat OK, Isaeva E, Sudhini YR, Knott B, Zhu K, Noben M, Suresh Kumar V, Endlich N, Mangos S, Reddy TV, Samelko B, Wei C, Altintas MM, Dryer SE, Sever S, Staruschenko A, Reiser JAuthor
Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsGlomerulosclerosis, Focal Segmental
Mice
Mice, Transgenic
Monomeric GTP-Binding Proteins
Podocytes
Proteinuria
TRPC Cation Channels
TRPC6 Cation Channel
Transcription Factors
