title: Kinesin 1 Drives Autolysosome Tubulation.
abstract: Autophagic lysosome reformation (ALR) plays an important role in maintaining lysosome homeostasis. During ALR, lysosomes are reformed by recycling lysosomal components from autolysosomes. The most noticeable step of ALR is autolysosome tubulation, but it is currently unknown how the process is regulated. Here, using an approach combining in vivo studies and in vitro reconstitution, we found that the kinesin motor protein KIF5B is required for autolysosome tubulation and that KIF5B drives autolysosome tubulation by pulling on the autolysosomal membrane. Furthermore, we show that KIF5B directly interacts with PtdIns(4,5)P2. Kinesin motors are recruited and clustered on autolysosomes via interaction with PtdIns(4,5)P2 in a clathrin-dependent manner. Finally, we demonstrate that clathrin promotes formation of PtdIns(4,5)P2-enriched microdomains, which are required for clustering of KIF5B. Our study reveals a mechanism by which autolysosome tubulation was generated.
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Du
authors.affiliation: State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Qian Peter
authors.initials: QP
authors.lastname: Su
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yueyao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yueguang
authors.initials: Y
authors.lastname: Rong
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Senyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.affiliation: School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Chuanmao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China; School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: sun_yujie@pku.edu.cn.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: liyulab@mail.tsinghua.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D001343:Autophagy; D002966:Clathrin / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008954:Models, Biological; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D051381:Rats
chemical_list: D002966:Clathrin; C521566:KIF5B protein, rat; D008081:Liposomes; D019269:Phosphatidylinositol 4,5-Diphosphate; D016547:Kinesins