Kappa opioid receptor contributes to EGF-stimulated neurite extension in development

Nien Pei Tsai, Yao Chen Tsui, John E. Pintar, Horace H Loh, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Epidermal growth factor (EGF), a mitogen, also stimulates neurite extension during development, but the underlying mechanism is elusive. This study reveals a functional role for kappa opioid receptor (KOR) in EGF-stimulated neurite extension, and the underlying mechanism. EGF and activated EGF receptor (EGFR) levels are elevated in embryonic spinal cords during late gestation stages, with concurrent rise in protein levels of KOR and axon extension markers, growth-associated protein 43 (GAP43), and transient axonal glycoprotein-1 (TAG-1). Both GAP43 and TAG-1 levels are significantly lower in KOR-null (KOR-/-) spinal cords,and EGFR in hibitors effectively reduce the levels of KOR, GAP43, and TAG-1 in wildtype embryonic spinal cords. For KOR -/- or KOR-knockdown dorsal root ganglion (DRG)neurons,EGF can no longer effectively stimulate axon extension, which can be rescued by introducing a constitutive KOR expressing vector but not by a regulated KOR vector carrying its 5′ untranslated region,which can be bound and repressed by growth factor receptor-bound protein 7 (Grb7). Furthermore, blocking KOR activation by application of anti-dynorphin,KOR antagonist, or EGFR inhibitor effectively reduces axon extension of DRG neurons. Thus, EGF-stimulated axon extension during development is mediated, at least partially, by specific elevation of KOR protein production at posttranscriptional level, as well as activation of KOR signaling. The result also reveals an action of EGF to augment posttranscriptional regulation of certain mRNAs during developmental stages.

Original languageEnglish (US)
Pages (from-to)3216-3221
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
DOIs
StatePublished - Feb 16 2010

Keywords

  • 5′ untranslated region
  • Dorsal root ganglion
  • Epidermal growth factor
  • Growth factor receptor-bound protein 7
  • Posttranscriptional regulation

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