Ministry of Education Key Laboratory of Protein Sciences, Tsinghua-Peking University Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Science, Tsinghua University, 100084, Beijing, China.
State Key Laboratory of Membrane Biology, Tsinghua-Peking University Joint Center for Life Sciences, School of Life Science, Tsinghua University, 100084, Beijing, China.
Nat Commun. 2019 Aug 16;10(1):3699. doi: 10.1038/s41467-019-11694-9.
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)P. 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.
WHAMM 是 Wiskott-Aldrich 综合征蛋白 (WASP) 家族的成员，是一种肌动蛋白成核促进因子 (NPF)，也与膜和微管相关。在这里，我们报告 WHAMM 是自噬溶酶体再形成 (ALR) 所必需的。WHAMM 敲除导致自噬溶酶体小管化受损，导致在长时间饥饿期间，大的自噬溶酶体积累。在机制上，WHAMM 通过其与 PI(4,5)P 的特异性相互作用被招募到自噬溶酶体膜上。然后，WHAMM 作为一种 NPF，促进肌动蛋白支架在自噬溶酶体表面的组装，以促进自噬溶酶体小管化。我们的研究表明，肌动蛋白支架在调节自噬溶酶体再形成中具有意想不到的作用。
