Regulation of Intracellular Transport

细胞器和颗粒的细胞内运输在动物细胞中普遍存在，并且具有基本的 重要的是这样的不同过程，如分泌，神经信号，组织内膜， 和细胞分裂。细胞内运输的驱动力由结合到细胞内的分子马达提供。 货物细胞器的表面和移动沿着微管（MT）和肌动蛋白丝（AF）。因为 几种类型的马达同时与同一种货物结合，同一种细胞器沿着运动 这两种类型的细胞骨架轨道运输事件必须被精确地调节，以确保 细胞器和颗粒到特定的细胞目的地，但确切的调控机制在很大程度上是 未知在这里，我们建议检查的机制，调节细胞内运输使用 黑色素细胞作为实验系统。这些细胞的主要功能是快速和同步 数以千计的膜结合的色素颗粒的重新分布，聚集在细胞中心或 通过细胞质内的移动使MT和AF沿着移动， 动力蛋白（聚集）和驱动蛋白2和肌球蛋白V（分散）。在这些电机之间切换， 细胞骨架系统受单个第二信使cAMP调节，并涉及蛋白质的活性。 激酶A（PKA）。PI的背景数据表明，PKA在细胞膜上形成两个单独的复合物。 颜料颗粒表面的分子马达参与了颜料的聚集和分散; 这些复合体被称为“调节运动单位”（RMU）。初步证据还表明， AF本身可能在色素转运中发挥积极作用。在这个研究项目中，生物化学，分子， 和细胞的方法将被用来测试的假设，多种机制参与了 调节黑色素细胞的细胞内运输。为了研究这些调节机制， 将确定RMU的组成部分，并阐明它们在分子马达调节中的作用。 细胞骨架轨道本身的性质在调节细胞内转运中的作用将被讨论。 也决心。

Intracellular transport of organelles and particles is ubiquitous in animal cells and has fundamental importance for such diverse processes as secretion, neuronal signaling, organization of endomembranes, and cell division. The driving force for intracellular transport is provided by molecular motors bound to the surface of cargo organelles and moving along microtubules (MTs) and actin filaments (AFs). Because several types of motors are simultaneously bound to the same cargo and the same organelles move along both types of cytoskeletal tracks transport events have to be precisely regulated to ensure the delivery of organelles and particles to specific cellular destinations but the exact regulatory mechanisms are largely unknown. Here we propose to examine the mechanisms of regulation of intracellular transport using melanophores as an experimental system. The major function of these cells is fast and synchronous redistribution of thousands of membrane-bounded pigment granules, which aggregate at the cell center or redisperse uniformly throughout the cytoplasm by moving along MTs and AFs by means of cytoplasmic dynein (aggregation), and kinesin 2 and myosin V (dispersion). Switching between these motors and cytoskeletal systems is regulated by a single second messenger, cAMP, and involves the activity of Protein Kinase A (PKA). Background data by the PI demonstrates that PKA forms two separate complexes on the surface of pigment granules with molecular motors involved in pigment aggregation and pigment dispersion; these complexes are called "regulated motor units" (RMU). Preliminary evidence also indicates that MTs and AFs themselves may play an active role in pigment transport. In this research project biochemical, molecular, and cellular approaches will be used to test the hypothesis that multiple mechanisms are involved in the regulation of intracellular transport in melanophores. To examine these regulatory mechanisms, signaling components of RMU will be identified, and their role in the regulation of molecular motors will be elucidated. The role of the properties of cytoskeletal tracks themselves in the regulation of intracellular transport will be also determined.