Mutations in Caenorhabditis elegans Cytoplasmic Dynein Components Reveal Specificity of Neuronal Retrograde Cargo

Sandhya P. Koushika, Anneliese M. Schaefer, Rose Vincent, John H. Willis, Bruce Bowerman, Michael L. Nonet

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

We describe Caenorhabditis elegans dynein complex mutants, which misaccumulate synaptic proteins at the ends of neuronal processes. Ultrastructural analysis revealed irregularly sized vesicles that likely represent accumulation of cargo. We propose that synaptobrevin, synaptotagmin, and UNC-104 are specific cargoes of the dynein complex. Many cargoes link to dynein via interactions between dynactin and vesicle-associated spectrin. However, loss of spectrin results in only mild and occasional defects in synaptobrevin localization. Thus, the dynein-dynactin complex shows neuronal cargo selectivity without spectrin being a critical component of cargo binding. We observed parallels to progressive motor neuron disease symptoms in these animals. With age, neuronal misaccumulations increase in size and frequency; locomotion becomes progressively slower; and life span is shortened. These mutants provide a model to assess whether defects in transport of specific cargo mediate neuronal dysfunction.

Original languageEnglish
Pages (from-to)3907-3916
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number16
DOIs
StatePublished - Apr 21 2004

Keywords

  • Axonal transport (axoplasmic transport)
  • Dynactin
  • Dynein
  • Retrograde
  • Spectrin
  • Synapse

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