REGULATION OF CYTOSKELETON AND MEMBRANE TRAFFIC BY P22

虽然有充分的文献证明，完整的微管是必需的， 膜运输的各个步骤， 微管参与亚细胞之间的货物运输 细胞器和质膜的连接仍然不完整。大部分 该领域的工作集中在微管马达介导的囊泡 运输，但很少有人知道其他，非微管马达 可能调控局部微管动力学的分子 膜运输到微管网络。 本研究的主要目的是研究其分子机制 将膜运输耦合到细胞骨架。我们先前已经 鉴定了预测分子量为22.3kDa的蛋白质，命名为p22， 其属于钙结合蛋白的EF-手超家族。我们 已经表明p22是膜运输所必需的，在我们的研究中， 初步数据表明，p22在体内与微管结合， 和体外培养。有趣的是，p22染色模式呈现点状， 沿着微管与它与区域相关联 沿着微管的囊泡运动。 基于其与信号转导物如钙调神经磷酸酶和 钙调素，我们目前对p22功能的模型是，p22作用于 通过将钙信号转导到下游来调节膜运输 效应器这些反过来又可能涉及到规范的附件， 膜到微管，在调节局部微管动力学或 在控制微管运动活动方面。这项研究概述了 应用将使我们能够揭示这种新蛋白质在 膜交通值得注意的是，p22是第一个确定的非- 马达蛋白可能通过其调节膜交通 与细胞骨架的联系。功能 p22的特性将是重要的理解细胞 像细胞迁移和细胞极性以及异常的 诸如肿瘤细胞对生长抑制剂和 刺激，已被证明是由动态和复杂的介导 细胞骨架重排和膜运输之间的相互作用。

Although it is well documented that intact microtubules are required for various steps of membrane traffic, the molecular mechanism of how microtubules participate in the transport of cargo between subcellular organelles and to the plasma membrane is still incomplete. Much of the work in the field has focused on microtubule motor-mediated vesicle transport, but little is known about other, non-microtubule motor molecules that might regulated localized microtubular dynamics of couple membrane traffic to the microtubule network. The main purpose of our research is the study of the molecular mechanisms coupling membrane traffic to the cellular cytoskeleton. We have previously identified a protein of 22.3 kDa predicted molecular mass, named p22, which belongs to the EF-hand super-family of calcium-binding proteins. We have shown that p22 is required for membrane traffic and in our preliminary data, we show that p22 associates with microtubules in vivo and in vitro. Interestingly, the p22 staining pattern appears punctate along the microtubules consistent with it being associated with regions of vesicular movement along the microtubules. Based on it structural homology to signal transducers as calcineurin and calmodulin, our current model for the function of p22 is that p22 acts to modulate membrane traffic by transducing calcium signals to downstream effectors. These in turn could be involved in regulating the attachment of membranes to microtubules, in modulating localized microtubule dynamics or in controlling microtubular motor activity. The research outlined in this application will allow us to reveal the role this novel protein plays in membrane traffic. Significantly, p22 is one of the first identified non- motor proteins that is likely to regulate membrane traffic through its association with the cellular cytoskeleton. The functional characterization of p22 will be important to the understanding of cellular processes like cell migration and cell polarity as well as of abnormal processes like tumor cell response to both growth inhibitors and stimulators, which have been shown to be mediated by dynamic and complex interactions between cytoskeletal rearrangements and membrane traffic.