title: Agrin regulates growth cone turning of Xenopus spinal motoneurons.
abstract: 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.
authors.affiliation: Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Amy K Y
authors.initials: AK
authors.lastname: Fu
authors.forename: Fanny C F
authors.initials: FC
authors.lastname: Ip
authors.forename: Chien-ping
authors.initials: CP
authors.lastname: Wu
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.forename: Mu-ming
authors.initials: MM
authors.lastname: Poo
authors.forename: Xiao-bing
authors.initials: XB
authors.lastname: Yuan
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
mesh_terms: 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
chemical_list: D018171:Agrin; D019869:Phosphatidylinositol 3-Kinases; D020830:rac1 GTP-Binding Protein