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Updated: Jun 28, 2025

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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 06269.

Molecular Biology of the Cell
|April 10, 2024
PubMed

Insights

The WHAMM protein is crucial for kidney function, aiding nutrient reabsorption and proper autophagy. Its absence in mice leads to kidney abnormalities and impaired cellular proteostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • The actin cytoskeleton is vital for eukaryotic cell functions.
  • Actin nucleation factors are not well understood at the organismal or disease level.
  • WHAMM (WD repeat protein interacting with NPHP4) is an actin nucleation factor.

Purpose of the Study:

  • To investigate the role of WHAMM in kidney physiology and cellular proteostasis.
  • To examine the impact of WHAMM inactivation in mice.

Main Methods:

  • Generated WHAMM knockout mice.
  • Analyzed kidney physiology, including nutrient excretion and structure.
  • Assessed autophagy markers (LC3) in kidney tissue and cultured cells.
  • Investigated WHAMM and Arp2/3 complex function in autophagosome dynamics in vitro.

Main Results:

  • WHAMM knockout mice showed increased excretion of albumin, glucose, phosphate, and amino acids.
  • Structural abnormalities in the kidney proximal tubules were observed in knockout mice.
  • Loss of WHAMM led to accumulation of lipidated LC3, indicating altered autophagy.
  • WHAMM and Arp2/3 complex are essential for autophagic membrane closure and cargo receptor recruitment in cells.

Conclusions:

  • WHAMM-mediated actin assembly is critical for maintaining kidney function, particularly nutrient reabsorption.
  • WHAMM plays a significant role in regulating autophagy and autophagosome membrane remodeling.
  • Dysregulation of WHAMM may contribute to kidney diseases involving impaired proteostasis.

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