Role of the Go/i signaling network in the regulation of neurite outgrowth.

Published

Conference Paper

Neurite outgrowth is a complex differentiation process stimulated by many neuronal growth factors and transmitters and by electrical activity. Among these stimuli are ligands for G-protein-coupled receptors (GPCR) that function as neurotransmitters. The pathways involved in GPCR-triggered neurite outgrowth are not fully understood. Many of these receptors couple to Galphao, one of the most abundant proteins in the neuronal growth cones. We have studied the Go signaling network involved in neurite outgrowth in Neuro2A cells. Galphao can induce neurite outgrowth. The CB1 cannabinoid receptor, a Go/i-coupled receptor expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating Rap1, which promotes the Galphao-stimulated proteasomal degradation of Rap1GAPII. CB1-receptor-mediated Rap1 activation leads to the activation of a signaling network that includes the small guanosine triphosphate (GTP)ases Ral and Rac, the protein kinases Src, and c-Jun N-terminal kinase (JNK), which converge onto the activation of signal transducer and activator of transcription 3 (Stat3), a key transcription factor that mediates the gene expression process of neurite outgrowth in Neuro2A cells. This review describes current findings from our laboratory and also discusses alternative pathways that Go/i might mediate to trigger neurite outgrowth. We also analyze the role neurotransmitters, which stimulate Go/i to activate a complex signaling network controlling neurite outgrowth, play in regeneration after neuronal injury.

Full Text

Duke Authors

Cited Authors

  • He, JC; Neves, SR; Jordan, JD; Iyengar, R

Published Date

  • July 2006

Published In

Volume / Issue

  • 84 / 7

Start / End Page

  • 687 - 694

PubMed ID

  • 16998532

Pubmed Central ID

  • 16998532

International Standard Serial Number (ISSN)

  • 0008-4212

Digital Object Identifier (DOI)

  • 10.1139/y06-025

Conference Location

  • Canada