Teng K K, Courtney J C, van Bergen en Henegouwen P, Birge R B, Hempstead B L
Division of Hematology-Oncology, Cornell University Medical College, New York, New York 10021, USA.
Mol Cell Neurosci. 1996;8(2-3):157-70.
Expression of the adaptor protein v-Crk in PC12 cells results in sustained activation of NGF signaling pathways and augmented neuritogenesis. However, the inhibitory effect of the v-Crk SH2 domain mutant on neurite elongation does not correlate with impaired Trk A dependent signaling events or gene induction. In contrast, immunofluorescence studies and Triton X-100 extraction experiments indicate that v-Crk co-localizes with the cytoskeletal protein paxillin in the actin cytoskeleton whereas the v-Crk SH2 mutant causes aberrant aggregration of actin filaments at the growth cones. Interestingly, the neurotrophin receptor p75 in v-CrkPC12 cells also displays enhanced localization to the cytoskeleton and these cells exhibit an increased rate of NGF internalization. Together our data suggest that v-Crk might target the NGF-activated receptor signaling complex to the cytoskeleton, thereby potentiating neuritogenesis at the growth cone level. However, mutation in the v-Crk SH2 domain uncouples NGF signaling from the cytoskeletal interactions necessary for neurite elongation.
衔接蛋白v-Crk在PC12细胞中的表达导致NGF信号通路的持续激活和神经突生成增加。然而，v-Crk SH2结构域突变体对神经突伸长的抑制作用与Trk A依赖性信号事件受损或基因诱导无关。相反，免疫荧光研究和Triton X-100提取实验表明，v-Crk与肌动蛋白细胞骨架中的细胞骨架蛋白桩蛋白共定位，而v-Crk SH2突变体导致生长锥处肌动蛋白丝异常聚集。有趣的是，v-Crk PC12细胞中的神经营养因子受体p75也显示出增强的细胞骨架定位，并且这些细胞表现出NGF内化率增加。我们的数据共同表明，v-Crk可能将NGF激活的受体信号复合物靶向细胞骨架，从而在生长锥水平增强神经突生成。然而，v-Crk SH2结构域的突变使NGF信号与神经突伸长所需的细胞骨架相互作用解偶联。
