Phospholipase C-gamma and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance.
Expression of rat TrkA in Xenopus spinal neurons confers responsiveness of these neurons to nerve growth factor (NGF) in assays of neuronal survival and growth cone chemotropism. Mutational analysis indicates that coactivation of phospholipase C-gamma (PLC-gamma) 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-gamma and PI3-kinase pathways.
Department of Biology, University of California at San Diego, La Jolla 92093, USA.
G
G
Ming
H
H
Song
B
B
Berninger
N
N
Inagaki
M
M
Tessier-Lavigne
M
M
Poo
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D003463:Cues; D003593:Cytoplasm / Q000502:physiology*; D020439:Growth Cones / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D000075388:Netrin-1; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051966:Phospholipase C gamma; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D010738:Type C Phospholipases / Q000502:physiology*; D014981:Xenopus
D007527:Isoenzymes; D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma