Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation

Douglas Simon Campbell, Christine E. Holt

Research output: Contribution to journalArticle

573 Citations (Scopus)

Abstract

Growth cones contain mRNAs, translation machinery, and, as we report here, protein degradation machinery. We show that isolated retinal growth cones immediately lose their ability to turn in a chemotropic gradient of netrin-1 or Sema3A when translation is inhibited. Translation inhibition also prevents Sema3A-induced collapse, while LPA-induced collapse is not affected. Inhibition of proteasome function blocks responses to netrin-1 and LPA but does not affect Sema3A responses. We further demonstrate in isolated growth cones that netrin-1 and Sema3A activate translation initiation factors and stimulate a marked rise in protein synthesis within minutes, while netrin-1 and LPA elicit similar rises in ubiquitin-protein conjugates. These results suggest that guidance molecules steer axon growth by triggering rapid local changes in protein levels in growth cones.

Original languageEnglish
Pages (from-to)1013-1026
Number of pages14
JournalNeuron
Volume32
Issue number6
DOIs
Publication statusPublished - 2001 Dec 20
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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