title: Nudel promotes axonal lysosome clearance and endo-lysosome formation via dynein-mediated transport.
abstract: Axonal transport is critical for neuronal function and survival. Cytoplasmic dynein and its accessory complex dynactin form a microtubule minus end-directed motor in charge of retrograde transport. In this study, we show that Nudel, a dynein regulator, was highly expressed in dorsal root ganglion (DRG) neurons. Microinjection of anti-Nudel antibody into cultured DRG neurons abolished retrograde transport of membranous organelles in the axon and led to dispersions of Golgi cisternae in the soma. As a result, lysosomes, which are normally enriched in the soma, moved persistently into and thus accumulated in axons. Endo-lysosome formation was also markedly delayed. As anterograde motility of mitochondria was not inhibited, the antibody apparently did not abolish retrograde transport by destructing axonal microtubule tracks. Similar results were obtained by microinjecting N-terminal Nudel, anti-dynein antibody or a p150(Glued) mutant capable of abrogating the dynein-dynactin association. These results indicate a critical role of Nudel in dynein-mediated axonal transport. Moreover, the effects of dynein on endolysosome formation and regional sequestration of lysosomes may contribute to defects in the endocytic pathway seen in neurons of patients or animals with malfunction of dynein.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qiangge
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fubin
authors.initials: F
authors.lastname: Wang
authors.forename: Jingli
authors.initials: J
authors.lastname: Cao
authors.forename: Yidong
authors.initials: Y
authors.lastname: Shen
authors.forename: Qiongping
authors.initials: Q
authors.lastname: Huang
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004398:Dyneins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008845:Microinjections; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; C486015:Ndel1 protein, mouse; D004398:Dyneins