VanBerkum M F, Goodman C S
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Neuron. 1995 Jan;14(1):43-56. doi: 10.1016/0896-6273(95)90239-2.
Ca(2+)-calmodulin (CaM) function was selectively disrupted in a specific subset of growth cones in transgenic Drosophila embryos in which a specific enhancer element drives the expression of the kinesin motor domain fused to a CaM antagonist peptide (kinesin-antagonist or KA, which blocks CaM binding to target proteins) or CaM itself (kinesin-CaM or KC, which acts as a Ca(2+)-binding protein). In both KA and KC mutant embryos, specific growth cones exhibit dosage-dependent stalls in axon extension and errors in axon guidance, including both defects in fasciculation and abnormal crossings of the midline. These results demonstrate an in vivo function for Ca(2+)-CaM signaling in growth cone extension and guidance and suggest that Ca(2+)-CaM may in part regulate specific growth cone decisions, including when to defasciculate and whether or not to cross the midline.
在转基因果蝇胚胎的特定生长锥亚群中，钙调蛋白（CaM）的功能被选择性破坏。在这些胚胎中，特定的增强子元件驱动与钙调蛋白拮抗剂肽融合的驱动蛋白运动结构域（驱动蛋白拮抗剂或KA，其可阻断钙调蛋白与靶蛋白的结合）或钙调蛋白本身（驱动蛋白-钙调蛋白或KC，其作为一种钙结合蛋白）的表达。在KA和KC突变胚胎中，特定的生长锥在轴突延伸中表现出剂量依赖性停滞以及轴突导向错误，包括成束缺陷和中线异常交叉。这些结果证明了钙-钙调蛋白信号在生长锥延伸和导向中的体内功能，并表明钙-钙调蛋白可能部分调节特定的生长锥决策，包括何时分散以及是否穿过中线。
