Advanced Search

Submit Manuscript

ADVANCE ONLINE PUBLICATION

ORIGINAL ARTICLES

Myosin 1D and the branched actin network control the condensation of p62 bodies

Xuezhao Feng1,2,† , Wanqing Du3,† , Mingrui Ding4,† , Wenkang Zhao3 , Xirenayi Xirefu1,2,5 , Meisheng Ma6 , Yuhui Zhuang7 , Xiaoyu Fu8 , Jiangfeng Shen7 , Jinpei Zhang1,2 , Xiuying Lei1,2 , Daxiao Sun3 , Qing Xi1,2 , Yiliyasi Aisa1,2,5 , Qian Chen1,2 , Ying Li3,9 , Wenjuan Wang9 , Shanjin Huang7 , Li Yu3 , Pilong Li4,* , Na Mi1,2,*

1State Key Laboratory of Pathogenesis, Prevention and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
2State Key Laboratory of Pathogenesis, Prevention and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
3State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
4Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
5College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, China
6Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
7Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing, China
8Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center of Biological Structures, School of Life Sciences, Tsinghua University, Beijing, China
9Center of Biomedical Analysis, Tsinghua University, Beijing, China
These authors contributed equally: Xuezhao Feng, Wanqing Du, Mingrui Ding
* Correspondence: Pilong Li(pilongli@mail.tsinghua.edu.cn)Na Mi(mina2a@163.com)

Biomolecular condensation driven by liquid–liquid phase separation (LLPS) is key to assembly of membraneless organelles in numerous crucial pathways. It is largely unknown how cellular structures or components spatiotemporally regulate LLPS and condensate formation. Here we reveal that cytoskeletal dynamics can control the condensation of p62 bodies comprising the autophagic adaptor p62/SQSTM1 and poly-ubiquitinated cargos. Branched actin networks are associated with p62 bodies and are required for their condensation. Myosin 1D, a branched actin-associated motor protein, drives coalescence of small nanoscale p62 bodies into large micron-scale condensates along the branched actin network. Impairment of actin cytoskeletal networks compromises the condensation of p62 bodies and retards substrate degradation by autophagy in both cellular models and Myosin 1D knockout mice. Coupling of LLPS scaffold to cytoskeleton systems may represent a general mechanism by which cells exert spatiotemporal control over phase condensation processes.

https://doi.org/10.1038/s41422-022-00662-6

FULL TEXT | PDF

Browse 134