Nudel promotes axonal lysosome clearance and endo-lysosome formation via dynein-mediated transport. Academic Article uri icon

Overview

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.

publication date

  • May 27, 2009

Research

keywords

  • Axonal Transport
  • Axons
  • Carrier Proteins
  • Dyneins
  • Endosomes
  • Lysosomes

Identity

Scopus Document Identifier

  • 68549111211

Digital Object Identifier (DOI)

  • 10.1111/j.1600-0854.2009.00945.x

PubMed ID

  • 19522757

Additional Document Info

volume

  • 10

issue

  • 9