Agrin regulates growth cone turning of Xenopus spinal motoneurons.
The pivotal role of agrin in inducing postsynaptic specializations at neuromuscular junctions has been well characterized. Increasing evidence suggests that agrin is also involved in neuronal development. In this study, we found that agrin inhibited neurite extension and, more importantly, a gradient of agrin induced repulsive growth-cone turning in cultured Xenopus spinal neurons. Incubation with a neutralizing antibody to agrin or expression of the extracellular domain of muscle-specific kinase, a component of the agrin receptor complex, abolished these effects of agrin. Agrin-induced repulsive growth-cone turning requires the activity of PI3-kinase and Ca2+ signaling. In addition, the expression of dominant-negative Rac1 inhibited neurite extension and blocked agrin-mediated growth-cone turning. Taken together, our findings suggest that agrin regulates neurite extension and provide evidence for an unanticipated role of agrin in growth-cone steering in developing neurons.
Xu
Xiaohua
X
Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China.
Fu
Amy K Y
AK
Ip
Fanny C F
FC
Wu
Chien-ping
CP
Duan
Shumin
S
Poo
Mu-ming
MM
Yuan
Xiao-bing
XB
Ip
Nancy Y
NY
D018171:Agrin / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000166:cytology; D020439:Growth Cones / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology* / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D018171:Agrin; D019869:Phosphatidylinositol 3-Kinases; D020830:rac1 GTP-Binding Protein