1. WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes
- Author
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Dai, Anbang, Yu, Li, and Wang, Hong-Wei
- Subjects
0301 basic medicine ,Lysosomal membrane ,Autolysosome ,Science ,education ,General Physics and Astronomy ,02 engineering and technology ,macromolecular substances ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Polymerization ,Gene Knockout Techniques ,03 medical and health sciences ,Microtubule ,Lysosome ,Autophagy ,medicine ,Animals ,Humans ,lcsh:Science ,Actin ,health care economics and organizations ,Actin nucleation ,Microscopy, Confocal ,Multidisciplinary ,Chemistry ,HEK 293 cells ,Membrane Proteins ,General Chemistry ,021001 nanoscience & nanotechnology ,Actins ,Rats ,Wiskott-Aldrich Syndrome Protein Family ,Cell biology ,Microscopy, Electron ,HEK293 Cells ,030104 developmental biology ,medicine.anatomical_structure ,Microscopy, Fluorescence ,lcsh:Q ,Lysosomes ,0210 nano-technology ,Microtubule-Associated Proteins - 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., After autophagic cargo degradation, autolysosomes undergo a reformation process to recycle lysosomal membrane components. Here, Dai et al. demonstrate that the actin nucleation promoting factor WHAMM is required for autolysosome reformation by providing an actin scaffold to drive tubulation.
- Published
- 2019