Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor

Eun Joo Song, Hye Min Hong, Young Sook Yoo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The ubiquitin-proteasome pathway regulates many biological processes, including protein degradation, receptor endocytosis, protein sorting, subnuclear trafficking and neuronal differentiation. While proteasome inhibition is known to induce neurite outgrowth, the signaling mechanisms that mediate these effects have not been defined. In this study, we investigated the underlying mechanisms that link proteasome inhibition with neurite generation. We found that the proteasome inhibitors, MG132 and lactacystin, induced neurite outgrowth and also activated extracellular signal-regulated kinase/mitogen activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways. These proteasome inhibitors also induced phosphorylation and ubiquitination of TrkA receptors, indicating that proteasome inhibition activates the major pathways of TrkA signaling. However, in contrast to nerve growth factor stimulation, which induces internalization of surface TrkA receptors, proteasome inhibitor-induced neurite outgrowth did not require TrkA receptor internalization. These results indicate that the ubiquitin-proteasome system regulates neurite formation through posttranslational modification of TrkA receptors.

Original languageEnglish
Pages (from-to)539-545
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume41
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • MG132
  • Neurite outgrowth
  • Proteasome inhibitor
  • TrkA receptor
  • Ubiquitination

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