Phospholipase C-γ and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance

Guo li Ming, Hong jun Song, Benedikt Berninger, Naoyuki Inagaki, Marc Tessier-Lavigne, Poo Mu-Ming

Research output: Contribution to journalArticle

Abstract

Expression of rat TrkA in Xenopus spinal neurons confers responsiveness of these neurons to nerve growth factor (NGF) in assays of survival and growth cone chemotropism. Mutational analysis indicates that coactivation of phospholipase C-γ (PLC-γ) and phosphoinositide 3-kinase (PI3-kinase) by specific cytoplasmic domains of TrkA is essential for triggering chemoattraction of the growth cone in an NGF gradient. Uniform exposure of TrkA-expressing neurons to NGF resulted in a cross-desensitization of turning responses induced by a gradient of netrin-1, brain-derived neurotrophic factor (BDNF), or myelin-associated glycoprotein (MAG) but not by a gradient of collapsin-1/semaphorin III/D or neurotrophin-3 (NT-3). These results, together with the effects of pharmacological inhibitors, support the notion that there are common cytosolic signaling pathways for two separate groups of guidance cues, one of which requires coactivation of PLC-γ and PI3-kinase pathways.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalNeuron
Volume23
Issue number1
DOIs
StatePublished - May 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Phospholipase C-γ and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance'. Together they form a unique fingerprint.

  • Cite this

    Ming, G. L., Song, H. J., Berninger, B., Inagaki, N., Tessier-Lavigne, M., & Mu-Ming, P. (1999). Phospholipase C-γ and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance. Neuron, 23(1), 139-148. https://doi.org/10.1016/S0896-6273(00)80760-6