WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes

Nat Commun. 2019 Aug 16;10(1):3699. doi: 10.1038/s41467-019-11694-9.

Abstract

WHAMM, a member of the Wiskott-Aldrich syndrome protein (WASP) family, is an actin nucleation promoting factor (NPF) that also associates with membranes and microtubules. Here we report that WHAMM is required for autophagic lysosome reformation (ALR). WHAMM knockout causes impairment of autolysosome tubulation, which results in accumulation of enlarged autolysosomes during prolonged starvation. Mechanistically, WHAMM is recruited to the autolysosome membrane through its specific interaction with PI(4,5)P2. WHAMM then works as an NPF which promotes assembly of an actin scaffold on the surface of the autolysosome to promote autolysosome tubulation. Our study demonstrates an unexpected role of the actin scaffold in regulating autophagic lysosome reformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Autophagy / genetics*
  • Cell Line
  • Gene Knockout Techniques
  • HEK293 Cells
  • Humans
  • Lysosomes / metabolism*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Polymerization
  • Rats
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / metabolism

Substances

  • Actins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • WHAMM protein, human
  • Wiskott-Aldrich Syndrome Protein Family