Lebrand Cecile, Dent Erik W, Strasser Geraldine A, Lanier Lorene M, Krause Matthias, Svitkina Tatyana M, Borisy Gary G, Gertler Frank B
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Neuron. 2004 Apr 8;42(1):37-49. doi: 10.1016/s0896-6273(04)00108-4.
Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/VASP proteins play a pivotal role in formation and elongation of filopodia along neurite shafts and growth cone. Netrin-1-induced filopodia formation was dependent upon Ena/VASP function and directly correlated with Ena/VASP phosphorylation at a regulatory PKA site. Accordingly, Ena/VASP function was required for filopodial formation from the growth cone in response to global PKA activation. We propose that Ena/VASP proteins control filopodial dynamics in neurons by remodeling the actin network in response to guidance cues.
Ena/VASP蛋白在轴突生长和导向中发挥重要作用。Ena/VASP活性调节成纤维细胞片状伪足内肌动蛋白网络的组装和几何形状。在生长锥中，Ena/VASP蛋白集中在丝状伪足尖端，但其在生长锥对导向信号反应中的作用尚未明确。我们发现Ena/VASP蛋白在沿神经突轴和生长锥的丝状伪足形成和伸长中起关键作用。Netrin-1诱导的丝状伪足形成依赖于Ena/VASP功能，并与调节性PKA位点的Ena/VASP磷酸化直接相关。因此，响应全局PKA激活，生长锥形成丝状伪足需要Ena/VASP功能。我们提出，Ena/VASP蛋白通过响应导向线索重塑肌动蛋白网络来控制神经元中的丝状伪足动力学。
