Hong-Wei Wang’s group and Li Yu’s group reported a new mechanism of branch actin network regulating autolysosome reformation

2019-08-20 17:51:02

On Aug 16, 2019, Professor Hong-Wei Wang’s group and Professor Li Yu’s group at School of Life Sciences, Tsinghua University published a research article in Nature Communications entitled “WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes”.

Autophagy is a conserved lysosome-based degradation pathway. In mammalian cells, autophagosomes were formed under stimulus such as starvation. The autophagosomes then fused with lysosomes to form autolysosomes for the degradation of their contents. The autolysosomes subsequently go through a process called autolysosome reformation (ALR), in which the lysosomal membrane components are recycled from autolysosomes to regenerate lysosomes1. Ever since the initial report on the discovery of ALR in 2010, Professor Yu’s group have made great efforts in uncovering the molecular mechanism governing ALR. Through a series of studies, Professor Yu’s group have revealed a PI(4,5)P2, Clathrin and KIF5B kinesin mediated machinery regulating ALR2, 3, laying a solid foundation of the understanding of ALR.

In the current work, PhD student Anbang Dai co-supervised by Professor Wang and Professor Yu first discovered an unexpected role of WHAMM in autolysosome reformation (ALR). They found that WHAMM co-localized with autolysosomes during prolonged starvation and further observed a defect in ALR in WHAMM-KO cells. They further revealed that, 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. This study demonstrates a novel role of the actin scaffold in regulating autophagic lysosome reformation, and shade new insights into the role of branch actin network in general membrane shaping processes.

Time lapse images of WHAMM on autolysosomes and a representative model of WHAMM’s role in ALR

This work was supported by grant (2016YFA0501100 to H.W.) from the Ministry of Science and Technology of China, grant (Z161100000116034 to H.W.) from the Beijing Municipal Science & Technology Commission.

 

Article link:https://doi.org/10.1038/s41467-019-11694-9

 

References:

1.         Yu, L. et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465, 942-946 (2010).

2.         Rong, Y. et al. Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nature Cell Biology 14, 924-934 (2012).

3.         Du, W. et al. Kinesin 1 Drives Autolysosome Tubulation. Developmental Cell 37, 326-336 (2016).