title: HookA is a novel dynein-early endosome linker critical for cargo movement in vivo.
abstract: Cytoplasmic dynein transports membranous cargoes along microtubules, but the mechanism of dynein-cargo interaction is unclear. From a genetic screen, we identified a homologue of human Hook proteins, HookA, as a factor required for dynein-mediated early endosome movement in the filamentous fungus Aspergillus nidulans. HookA contains a putative N-terminal microtubule-binding domain followed by coiled-coil domains and a C-terminal cargo-binding domain, an organization reminiscent of cytoplasmic linker proteins. HookA-early endosome interaction occurs independently of dynein-early endosome interaction and requires the C-terminal domain. Importantly, HookA interacts with dynein and dynactin independently of HookA-early endosome interaction but dependent on the N-terminal part of HookA. Both dynein and the p25 subunit of dynactin are required for the interaction between HookA and dynein-dynactin, and loss of HookA significantly weakens dynein-early endosome interaction, causing a virtually complete absence of early endosome movement. Thus, HookA is a novel linker important for dynein-early endosome interaction in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Rongde
authors.initials: R
authors.lastname: Qiu
authors.forename: Herbert N
authors.initials: HN
authors.lastname: Arst
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Peñalva
authors.forename: Xin
authors.initials: X
authors.lastname: Xiang
mesh_terms: D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D002874:Chromosome Mapping; D004398:Dyneins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025301:Hyphae / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D016547:Kinesins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport
chemical_list: D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D004398:Dyneins; D016547:Kinesins