title: Discovery of a vezatin-like protein for dynein-mediated early endosome transport.
abstract: Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. This abnormal accumulation depends on kinesin-3 and is due to a decrease in the frequency but not the speed of dynein-mediated early endosome movement. VezA-GFP signals are enriched at the hypha tip in an actin-dependent manner but are not obviously associated with early endosomes, thus differing from the early endosome association of the cargo adapter HookA (Hook in A. nidulans). On loss of VezA, HookA associates normally with early endosomes, but the interaction between dynein-dynactin and the early-endosome-bound HookA is significantly decreased. However, VezA is not required for linking dynein-dynactin to the cytosolic ∆C-HookA, lacking the cargo-binding C-terminus. These results identify VezA as a novel regulator required for the interaction between dynein and the Hook-bound early endosomes in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences-F. Edward Hébert School of Medicine, Bethesda, MD 20814.
authors.forename: Xuanli
authors.initials: X
authors.lastname: Yao
authors.affiliation: Microbiology Section, Department of Medicine, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Herbert N
authors.initials: HN
authors.lastname: Arst
authors.affiliation: School of Plant Sciences, University of Arizona, Tucson, AZ 85721.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences-F. Edward Hébert School of Medicine, Bethesda, MD 20814 xin.xiang@usuhs.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiang
mesh_terms: D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D025301:Hyphae / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000072159:Dynactin Complex; D005656:Fungal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D056445:Cytoplasmic Dyneins; D004398:Dyneins; D016547:Kinesins