Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor

Title
Proteasome inhibition induces neurite outgrowth through posttranslational modification of TrkA receptor
Authors
송은주홍혜민유영숙
Keywords
Neurite Outgrowth; Proteasome inhibitor; TrkA receptor; MG132; Ubiquitination
Issue Date
2009-03
Publisher
The international journal of biochemistry & cell biology
Citation
VOL 41, NO 3, 539-545
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 outgrowthand 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.
URI
http://pubs.kist.re.kr/handle/201004/35056
ISSN
1357-2725
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KIST Publication > Article
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