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 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.
Subject(s)
Actins , Autophagosomes , Autophagy , Kidney , Mice, Knockout , Animals , Mice , Actins/metabolism , Autophagy/physiology , Humans , Autophagosomes/metabolism , Kidney/metabolism , Male , Kidney Tubules, Proximal/metabolism , Actin Cytoskeleton/metabolism , Actin-Related Protein 2-3 Complex/metabolism , Membrane Proteins/metabolism , Microtubule-Associated Proteins/metabolism , Polymerization , Fibroblasts/metabolismABSTRACT
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.
ABSTRACT
Biomedical waste is a well-recognized environmental problem, yet less is known about the waste generated in the delivery of veterinary care compared to human medicine. The objective of this project was to develop and pilot a waste audit protocol for veterinary medicine that could inform waste management at a US university veterinary teaching hospital and the broader veterinary community. We conducted a multi-day review of the Colorado State University Veterinary Teaching Hospital's small animal surgery and anesthesia units to measure the types and amounts of waste generated during routine surgeries. Metrics included total weight, number of bags, and individual counts for specific items of concern and items with sustainable alternatives. We calculated frequencies and percentages of waste by waste audit material category and noted any erroneous materials sorted. Despite waste being a prioritized sustainability issue in veterinary medicine, this work highlighted opportunities for better education on managing and optimizing existing resources through behavior modification. This article explores ways the 5Rs (Rethink, Reduce, Reuse, Recycle, Research) could be better operationalized in veterinary hospitals.
