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WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo

Alyssa M Coulter1, Valerie Cortés2, Corey J Theodore1

  • 1Department of Molecular & Cell Biology, Institute for Systems Genomics; University of Connecticut, Storrs CT, USA.

Biorxiv : the Preprint Server for Biology
|February 8, 2024
PubMed

Insights

The actin nucleation factor WHAMM is crucial for kidney function, impacting nutrient reabsorption and cellular autophagy. Its inactivation in mice leads to kidney abnormalities and impaired proteostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • The actin cytoskeleton is vital for eukaryotic cell functions, but its nucleation factors are poorly understood, especially in disease contexts.
  • The WHAMM protein is an actin nucleation factor whose organismal functions remain largely uncharacterized.

Approach:

  • Investigated the impact of WHAMM gene inactivation on mouse kidney physiology and cellular proteostasis.
  • Utilized WHAMM knockout mice and examined kidney tissue, fibroblasts, and human proximal tubule cells.
  • Analyzed nutrient excretion, kidney structure, and autophagy markers like LC3.

Key Points:

  • WHAMM knockout male mice showed increased excretion of albumin, glucose, phosphate, and amino acids, with proximal tubule abnormalities.
  • Loss of WHAMM in kidney tissue correlated with accumulation of lipidated LC3, suggesting autophagy defects.
  • WHAMM, with the Arp2/3 complex, regulates autophagic membrane closure and cargo receptor recruitment in cellular models.

Conclusions:

  • WHAMM-mediated actin assembly is essential for maintaining kidney function, particularly nutrient reabsorption.
  • WHAMM plays a critical role in autophagosome membrane remodeling and cellular proteostasis.
  • Understanding WHAMM's function provides insights into kidney diseases and cellular mechanisms of autophagy.

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