title: HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes.
abstract: Hermansky-Pudlak syndrome 6 protein (HPS6) has originally been identified as a subunit of the BLOC-2 protein complex that is involved in the biogenesis of lysosome-related organelles. Here, we demonstrate that HPS6 directly interacts with the dynactin p150(Glued) subunit of the dynein-dynactin motor complex and acts as cargo adaptor for the retrograde motor to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Small interfering RNA (siRNA)-mediated knockdown of HPS6 in HeLa cells not only partially blocks centripetal movement of lysosomes but also causes delay in lysosome-mediated protein degradation. Moreover, lysosomal acidification and degradative capacity, as well as fusion between late endosomes and/or multivesicular bodies and lysosomes are also impaired when HPS6 is depleted, suggesting that perinuclear positioning mediated by the dynein-dynactin motor complex is required for lysosome maturation and activity. Our results have uncovered a so-far-unknown specific role for HPS6 in the spatial distribution of the lysosomal compartment.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China jjliu@genetics.ac.cn.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D000072159:Dynactin Complex; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D020798:Two-Hybrid System Techniques
chemical_list: C000606360:DCTN1 protein, human; C000606364:Dctn1 protein, mouse; D000072159:Dynactin Complex; C493901:HPS6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins
keywords: DCTN1; HPS6; dynein–dynactin motor complex; lysosome; p150Glued