ORGANELLE MOVEMENT IN FAST AXONAL TRANSPORT

这个项目的目标是了解膜结合细胞器 在快速轴突运输过程中在神经元突起中移动。 两个ATP酶， 驱动蛋白和动力蛋白，被认为是运动的动力蛋白 膜结合细胞器沿着微管在快速轴突 运输 驱动蛋白被认为是细胞器的发动机 在顺行方向上的运输（从细胞体到细胞体） 突触末端），而动力蛋白在逆行中移动细胞器 方向，从终端到细胞体。 然而，许多细节 关于细胞器顺向和逆向运动的协调 仍有待解释。 一个基本的缺失是理解 膜相关动力蛋白是如何运输到突触末端的 而不干扰顺行运动。 是合理的 提出动力蛋白的运动活动是受调节的。 至少两 可以提出机制来解释这种调节：（1）a 动力蛋白的翻译后修饰可以使其开启和关闭， （2）特异性调节多肽冷调节细胞内的蛋白质。 动力蛋白的功能状态，将被确定，反映了 神经元胞质动力蛋白的不同功能状态，将是 通过表征来自坐骨神经的顺行和逆行动力蛋白来测试 神经阻滞和其他轴突运输模型系统。 以确定是否 观察到的差异有助于调节电机 动力蛋白的活性、不同形式动力蛋白的功能特性 将测量动力蛋白，包括ATP酶活性。 功能 观察到的磷酸化差异的意义 测量顺行和全细胞动力蛋白多肽。 的 将研究动力蛋白与膜结合细胞器的结合 在体内和体外。 抗哺乳动物脑细胞质动力蛋白抗体 将被用作动力蛋白功能的抑制探针， 挤压轴浆模型系统。

The goal of this project is to understand how membrane bounded organelles move in neuronal process during fast axonal transport. Two ATPases, kinesin and dynein, are proposed to be the motor proteins the movement of membrane bonded organelles along microtubules in fast axonal transport. It is believed that kinesin is the motor for organelle transport in the anterograde direction (from the cell body to the synaptic terminal) while dynein moves organelles in the retrograde direction, from the terminal to the cell body. However, many details about the coordination of anterograde and retrograde organelle movements remains to be explained. One basic missing component is an understanding of how membrane associated dynein is transported to the synaptic terminal without interfering with anterograde movement. It is reasonable to propose that the motor activity of dynein is regulated. At least two mechanisms can be proposed to account for such regulation:(1) a posttranslational modification of dynein could turn it on and off as necessary; or (2) specific regulatory polypeptides cold modulated the functional state of dynein, will be identified which reflect the different functional states of neuronal cytoplasmic dynein, will be tested by characterizing anterograde and retrograde dynein from sciatic nerve blocks and other axonal transport model systems. To determine if the observed differences contribute to the regulation of the motor activity of dynein, the functional properties of the different forms of dynein will be measured, including ATPase activity. The functional significance of observed differences in the phosphorylation of anterograde and whole cells dynein polypeptides will be measured. The association of dynein with membrane bounded organelles will be studied in vivo and in vitro. Antibodies to mammalian brain cytoplasmic dynein will be used as inhibitory probes of the function of dynein in the extruded axoplasm model system.