biostudies-literatureCoulter AMNIDDK NIH HHSNIA NIH HHSNIEHS NIH HHSNIGMS NIH HHSar80https://www.ebi.ac.uk/biostudies/studies/S-EPMC11238085biostudies-literatureUnknown35(6)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 <i>Whamm</i> 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 tubule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tissue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal membrane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and humaMolecular biology of the cellWHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.PMC11238085K02 AG050774P30 AG038070R01 DK131019R01 DK131061R01 ES029916R01 GM107441Cianciolo REKorstanje RCampellone KGCoulter AMTheodore CJCortes VfalseWHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.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 <i>Whamm</i> 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 tubule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tissue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal membrane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and huma2024-01-01T00:00:00Z2024 Jun2025-04-26T22:24:51.861Z2025-04-06T17:11:14.781ZS-EPMC112380853859829310.1091/mbc.E24-01-0025