Volume 32, No 7, Jul 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 7, July 2022: 659-669

ORIGINAL ARTICLES

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

Xuezhao Feng^1,2,† , Wanqing Du^3,† , Mingrui Ding^4,† , Wenkang Zhao³ , Xirenayi Xirefu^1,2,5 , Meisheng Ma⁶ , Yuhui Zhuang⁷ , Xiaoyu Fu⁸ , Jiangfeng Shen⁷ , Jinpei Zhang^1,2 , Xiuying Lei^1,2 , Daxiao Sun³ , Qing Xi^1,2 , Yiliyasi Aisa^1,2,5 , Qian Chen^1,2 , Ying Li^3,9 , Wenjuan Wang⁹ , Shanjin Huang⁷ , Li Yu³ , Pilong Li^4,* , Na Mi^1,2,*

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

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