MICROTUBULES AND REGULATION OF FOCAL CONTACTS

焦点接触是细胞的主要结构特化。 与黏附有关的膜和皮质肌动蛋白细胞骨架 培养的细胞到基质中；然而，人们对 控制其发育的细胞骨架机制。初步数据， 由莫斯科的该组织通过微管解聚药物获得 结果导致假设微管系统可能控制 通过管理国家机构的状况组织协调联络人 肌动蛋白皮质。反过来，由大脑皮层产生的收缩力量 它们作用于病灶的细胞骨架附着的膜蛋白 联系人会受到影响。这个项目的目标是研究 微管系统在焦点接触发育中的作用。具体目标 包括对震源结构和动力学变化的分析 特定改变干预措施后培养成纤维细胞中的接触 微管系统的结构和功能。这些问题包括暴露于 细胞对药物解聚或稳定微管的作用 作为微管运动蛋白抗体的注射，激动素。二 将使用补充技术来评估焦点的状态 接触：干涉-反射显微镜显示这些接触在 鉴定蛋白质的活细胞和免疫细胞化学方法 特别定位于焦点接触者和其他细胞骨架 蛋白质。为了测试大脑皮层收缩力量的变化 由微管特异剂诱导并与这些改变相关 随着焦点接触法的发展，力的测量方法也随之发展。 将在教堂山实验室使用。 计划中的实验将有助于更好地理解 细胞骨架调控细胞基质形成的机制 粘连。该项目将探索改变的性质在 细胞骨架-膜-基质关系在病理中的作用 肿瘤细胞的黏附和运动。

Focal contacts are the main structural specializations of the cell membrane and of cortical actin cytoskeleton responsible for the adhesion of cultured cells to the substratum; however, little is known about the cytoskeletal mechanisms controlling their development. Preliminary data, obtained by the group in Moscow, with microtubule-depolymerizing drugs resulted in the hypothesis that the microtubule system may control the organization of focal contacts via the regulation of the state of the actin cortex. In turn, the contractile forces developed by the cortex which act on the cytoskeleton-attached membrane proteins of the focal contacts are affected. The goal of this project is to study the role of microtubular system in the development of focal contacts. Specific aims include the analysis of the alterations of structure and dynamics of focal contacts in cultured fibroblasts after interventions specifically changing the structure and function of microtubular system. These include exposure of cells to the drugs depolymerizing or stabilizing microtubules as well as injection of antibody to microtubule motor protein, kinesin. Two complementary technologies will be used to assess the state of focal contacts: interference-reflection microscopy to reveal these contacts in living cells and immunocytochemical methods to identify proteins specifically localized in the focal contacts and for other cytoskeletal proteins. To test the alterations of contractile forces in the cortex induced by microtubule-specific agents and to correlate these alterations with those of focal contacts the methods of force measurements developed in the Chapel Hill laboratory will be used. The planned experiments will lead to better understanding of the mechanisms of cytoskeletal control of the formation of cell-matrix adhesions. The project will explore the nature of alterations in the cytoskeleton-membrane-matrix relationships responsible for pathological adhesion and motility of neoplastic cells.