WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration
Year: 2024
Type: article
Abstract: 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 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 human proximal tubule cells, WHAMM and its binding partner the Arp2/3 complex control autophagic membrane closure and cargo receptor recruitment. These results reveal a role for WHAMM-mediated actin assembly in maintaining kidney function and promoting proper autophagosome membrane remodeling.
Source: Molecular Biology of the Cell
Institutions: University of Connecticut, Jackson Laboratory, UConn Health
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Cytoskeletal control of membrane remodeling, Cytoskeletal functions in cell aging and disease, Genetic Factors that Influence Arsenic Toxicity, G9000145590, Causal connections between axon guidance proteins and early progressive kidney function decline in diabetes, Identification of Kidney Disease Modifier Genes in Mouse and Human Alport Syndrome, Nathan Shock Center for Excellence in Basic Biology of Aging
OpenAlex ID: W4394688589