MOLECULAR CONTROL OF CNS GROWTH AND REGENERATION

拟议的研究计划集中在以下分子机制上 调节轴突的矢量生长，特别是局部控制 生长锥体的质膜扩张和细胞骨架动力学。这 实验室最近证实，质膜的扩张在 生长锥体是一种受调节的现象，并发现了一种假定的、新颖的 可能参与其控制的信令级联。瀑布 涉及磷脂酶A2对磷脂酰肌醇二磷酸的裂解， 产生花生四烯酸和溶多磷肌醇。激活 磷脂酶A2及其产物的功能将用 以胎鼠脑内分离的生长锥为原代细胞 实验系统及一系列细胞生物学和生化 技巧。主要目标是：(1)建立解放军与 受体及其配体的分离；(Ii)研究其可能的功能 溶多磷脂酰肌醇作为FusoGen在膜扩张和细胞分裂中的作用(S) 作为肌动蛋白结合或其他细胞内生长锥蛋白的配基； (Iii)调查圆锥体和作为膜FusoGen；(Iv)相互关联 从完整生长看质膜扩张和生长锥运动 在无细胞系统中产生生化数据的培养中的锥体 被其他目标所取代。这些研究将导致对 调节局部生长锥推进和行为的机制和 预计会导致改变这些的因子(S)的分离 功能。

The proposed research program is focused on the molecular mechanisms that regulate vectorial growth of the neurite, especially, the local control of plasmalemmal expansion and cytoskeletal dynamics at the growth cone. This laboratory has demonstrated recently that plasmalemmal expansion at the growth cone is a regulated phenomenon and has discovered a putative, novel signalling cascade that may participate in its control. The cascade involves cleavage of phosphatidylinositol bisphosphate by phospholipase A2, generating arachidonic acid and lysopolyphosphoinositide. Activation of phospholipase A2 and the functions of its products will be analyzed using growth cones isolated from fetal rat brain (GCPs) as the primary experimental system and a series of cell biological and biochemical techniques. The major aims are: (i) to establish the link of PLA2 with a receptor and isolate its ligand; (ii) to study the possible functional role(s) of lysopolyphosphoinositide as a fusogen in membrane expansion and as a ligand for actin-binding or other intracellular growth cone proteins; (iii) to investigate the cones and as a membrane fusogen; (iv) to correlate plasmalemmal expansion and growth cone motility viewed in intact growth cones in culture with the biochemical data generated in cell-free systems by the other aims. These studies will lead to new insights into the mechanisms that regulate locally growth cone advancement and behavior and are expected to result in the isolation of factor(s) that modify these functions.