TY - JOUR
T1 - The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5
AU - Polat, Onur K.
AU - Isaeva, Elena
AU - Sudhini, Yashwanth R.
AU - Knott, Brenna
AU - Zhu, Ke
AU - Noben, Manuel
AU - Suresh Kumar, Varsha
AU - Endlich, Nicole
AU - Mangos, Steve
AU - Reddy, Tejasree Vallapu
AU - Samelko, Beata
AU - Wei, Changli
AU - Altintas, Mehmet M.
AU - Dryer, Stuart E.
AU - Sever, Sanja
AU - Staruschenko, Alexander
AU - Reiser, Jochen
N1 - Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Rac1
KW - TRPC5
KW - calcium
KW - focal segmental glomerulosclerosis
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U2 - 10.1016/j.kint.2023.01.016
DO - 10.1016/j.kint.2023.01.016
M3 - Article
C2 - 36750145
AN - SCOPUS:85148731140
SN - 0085-2538
VL - 103
SP - 1056
EP - 1062
JO - Kidney International
JF - Kidney International
IS - 6
ER -