神经元突起生长发育是神经修复、再生及神经组织工程学的重要研究内容，而生长锥的生长与坍塌又是神经突起发育的关键事件。然而对该事件的细胞内调节机制知之甚少。我们前期研究证实，PKCε参与了生长锥的坍塌过程，shRNA 干扰大鼠海马神经元PKCε后能抑制生长锥坍塌；此外PDLIM5蛋白与PKCε呈钙离子浓度依赖性结合，帮助PKCε转位。有研究表明PDLIM5在心肌/骨骼肌细胞内可与actin骨架蛋白相互作用，从而参与了细胞生长与运动的调控。因此我们提出PDLIM5及PDLIM5-PKCε复合物可能调控生长锥发育的科学假说。本项目拟采用小分子干扰、点突变、pulldown、荧光影像及钙成像等技术，获得PDLIM5参与生长锥坍塌过程的直接证据，并阐明PDLIM5及PDLIM5-PKCε复合物在调节生长锥及神经元突起生长中的作用。为揭示神经元生长发育过程以及寻找神经组织再生的新靶标提供可靠实验依据。

Growth and development of neurite is one of major aspects in nervous repair, regeneration and tissue engineering. The outgrowth and collapse of the growth cone plays critical role in the developing of neurite. However, little is known on the regulation mechanism of this key event in neuron. Our previous studies revealed that PKCε participates in the collapse of growth cone, and interference of PKCε with specific shRNA inhibits PMA induced hippocampal neuron growth cone collapse. Our further studies have indicated that PDLIM5 can bind PKCε specifically and plays as a cargo in the translocation of PKCε. Other research data showed that PDLIM5 could interacts with several cytoskeleton proteins, such as actin, in cardiomyocytes and skeletal muscle cells. Therefore, we assume a hypothesis that PDLIM5 and the PDLIM5-PKCε complex participate in the regulation of neural growth cone. We intend to use the shRNA interference, point mutation, pulldown assay,immunostaining and calcium imaging approaches, to prove that PDLIM5 participates in the collapse of the growth cone and identify the effect of PDLIM5 and PKCε on the regulation of the neurite outgrowth. The study results may reveal the mechanisms of neural growth and development mediated by the PDLIM5 and provides some candidate targets for nervous tissue engineering... .Keywords：PDLIM5, growth cone, scaffold protein, PKCε, signal transduction