Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor

Eun Joo Song, Hye Min Hong, Young Sook Yoo

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16 Scopus citations


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
Issue number3
StatePublished - Mar 2009

Bibliographical note

Funding Information:
We wish to thank to Louis Reichardt for generously providing anti-TrkA serum, Marie W. Wooten for kindly providing HA-tagged TrkA construct and Anne J. Charlton for English proofreading and helpful comments on the manuscript. This work was supported by grants from the Korea Ministry of Science and Technology (Systems Biology Research Grant; 2N30370).


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


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