REGULATION OF CYTOSKELETON AND MEMBRANE TRAFFIC BY P22

尽管有很好的证据表明，完整的微管是 膜运输的各个步骤，其分子机制是如何 微管参与亚细胞间的货物运输 细胞器和质膜仍不完整。世界上大部分的 该领域的工作主要集中在微管运动介导的囊泡上。 运输，但对其他非微管马达知之甚少 可能调节夫妇局部微管动力学的分子 膜运输到微管网络。 我们研究的主要目的是研究分子机制。 将膜交通与细胞细胞骨架连接起来。我们之前已经 鉴定出一种预测分子质量为22.3 kDa的蛋白质，命名为p22， 它属于钙结合蛋白的EF-Hand超家族。我们 已经证明p22是膜运输所必需的，在我们的 初步数据显示，p22在体内与微管相关。 而且是在体外。有趣的是，p22染色图案呈点状。 沿着与其一致的微管与 沿微管的囊泡运动。 在此基础上，与钙调神经磷酸酶和钙调神经磷酸酶等信号转导分子的结构同源性 钙调素，我们目前对p22功能的模型是p22作用于 通过向下游传递钙信号来调节膜交通 效应器。这些反过来可能涉及到调节依附于 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 应用程序将使我们能够揭示这种新的蛋白质在 膜流量。值得注意的是，p22是最早发现的非 可能通过其调节膜运输的马达蛋白 与细胞骨架有关。功能界别 P22的特性对于理解细胞 细胞迁移和细胞极性以及异常的过程 肿瘤细胞对生长抑制剂和 刺激物，已被证明是由动态和复杂的 细胞骨架重排和膜交通之间的相互作用。

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.