Document Type
Article
Publication Date
6-1-2024
Original Citation
Coulter A,
Cortés V,
Theodore C,
Cianciolo R,
Korstanje R,
Campellone K.
WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration. Mol Biol Cell. 2024;35(6):ar80.
Keywords
JMG, SS1, Animals, Mice, Actins, Autophagy, Mice, Knockout, Humans, Autophagosomes, Kidney, Male, Kidney Tubules, Proximal, Actin Cytoskeleton, Actin-Related Protein 2-3 Complex, Membrane Proteins, Microtubule-Associated Proteins, Polymerization, Fibroblasts
JAX Source
Mol Biol Cell. 2024;35(6):ar80.
ISSN
1939-4586
PMID
38598293
DOI
https://doi.org/10.1091/mbc.E24-01-0025
Grant
R.K. was sup- ported by National Institutes of Health grants ES29916, AG038070, DK131019, and DK131061, and the Alport Syndrome Foundation
Abstract
The actin cytoskeleton is essential for many functions of eukaryotic cells, but the factors that nucleate actin assembly are not well understood at the organismal level or in the context of disease. To explore the function of the actin nucleation factor WHAMM in mice, we examined how Whamm inactivation impacts kidney physiology and cellular proteostasis. We show that male WHAMM knockout mice excrete elevated levels of albumin, glucose, phosphate, and amino acids, and display structural abnormalities of the kidney proximal tu- bule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tis- sue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal mem- brane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and human proximal tubule cells, WHAMM and its binding partner the Arp2/3 complex control autopha- gic membrane closure and cargo receptor recruitment. These results reveal a role for WHAMM-mediated actin assembly in maintaining kidney function and promoting proper au- tophagosome membrane remodeling.
Creative Commons License
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