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The loss of profilin1 is catastrophic to podocytes
Sandeep K. Mallipattu
Sandeep K. Mallipattu
Published December 15, 2023
Citation Information: J Clin Invest. 2023;133(24):e175594. https://doi.org/10.1172/JCI175594.
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Commentary

The loss of profilin1 is catastrophic to podocytes

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Abstract

Profilin1 belongs to a family of small monomeric actin-binding proteins with diverse roles in fundamental actin-dependent cellular processes required for cell survival. Podocytes are postmitotic visceral epithelial cells critical for the structure and function of the kidney filtration barrier. There is emerging evidence that the actin-related mode of cell death known as mitotic catastrophe is an important pathway involved in podocyte loss. In this issue of the JCI, Tian, Pedigo, and colleagues demonstrate that profilin1 deficiency in podocytes triggered cell cycle reentry, resulting in abortive cytokinesis with a loss in ribosomal RNA processing that leads to podocyte loss and glomerulosclerosis. This study demonstrates the essential role of actin dynamics in mediating this fundamental mode of podocyte cell death.

Authors

Sandeep K. Mallipattu

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Figure 1

Profilins have a critical role in actin dynamics and preventing mitotic catastrophe.

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Profilins have a critical role in actin dynamics and preventing mitotic ...
(A) Profilins have a role in sequestering globular actin (G-actin) monomers and replenishing the ATP-actin monomer pool (dark green), so G-actin monomers can be assembled into F-actin in a concentration-dependent manner. During actin polymerization, ATP-actin is assembled into F-actin, and it is subsequently hydrolyzed by ATPase, leading to the conversion of ADP-actin. Actin depolymerization occurs at the end of the filament with the release of ADP-actin. (B) Profilin loss induces dsDNA damage, triggering chromatin instability and subsequent cell cycle reentry in podocytes. Subsequently, this leads to defective cytokinesis, cell detachment, and eventual mitotic catastrophe.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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