TY - JOUR
T1 - Phospholipase C-γ and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance
AU - Ming, Guo li
AU - Song, Hong jun
AU - Berninger, Benedikt
AU - Inagaki, Naoyuki
AU - Tessier-Lavigne, Marc
AU - Mu-Ming, Poo
PY - 1999/5
Y1 - 1999/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033136287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033136287&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80760-6
DO - 10.1016/S0896-6273(00)80760-6
M3 - Article
C2 - 10402200
AN - SCOPUS:0033136287
SN - 0896-6273
VL - 23
SP - 139
EP - 148
JO - Neuron
JF - Neuron
IS - 1
ER -