REGULATION OF CELL DIVISION

超出空间 但前提是。 这项研究的长期目标不变。我们的目标是确定分子 细菌细胞分裂的机制及其潜在的空间和时间调控 机械装置。我们的工作重点是FtsZ蛋白，它组装成一个细胞骨架环， 将其他蛋白质招募到组织站点。FtsZ是真核细胞微管蛋白和 在细胞周期中经历动态组装。它是几种内源性抑制物的靶点 作为正常细胞周期的一部分或对DNA损伤的反应，参与细胞分裂的调节。 我们最近的工作表明，Sula和Minc是FtsZ组装的抑制剂，然而，它们的功能相当 不同的。秀拉是在DNA损伤和隔离剂FtsZ阻止其组装后合成的。在……里面 相比之下，Minc是复杂的空间调节系统的一部分，该系统在细胞的两极之间振荡 以防止FtsZ在电池杆附近聚集。在体外，Minc可以阻止FtsZ组装并通过以下方式发挥作用 不稳定的FtsZ长丝。在体内，Minc要求Minc成为一种功能抑制物。思想通过以下方式激活Minc 将其招募到膜上，并赋予它对隔膜成分的高亲和力。我们的研究已经 证明了思维通过C端的两亲性螺旋与膜结合。我们还有 研究表明，Mine可以取代MinCD囊泡复合体中的Minc，并刺激大脑ATPase 从水泡中释放思想。我们还表明，大脑可以在小泡上聚合，从而导致 插管。我们的研究还确定了Minc上参与其与Mind结合和与其结合的位点 进入隔膜。在本提案中，我们将使用遗传和生化方法来进一步定义 Min蛋白之间以及Min蛋白与FtsZ之间的相互作用是调控所必需的 细胞分裂。我们还将利用从研究E.线圈最小系统中获得的知识来探索 枯草杆菌MIN系统和PAR蛋白。

EXCEED THE SPACE PROVIDED. The long term objectives of this research remain unchanged. The goals are to determine the molecular mechanisms involved in bacterial cell division and the underlying spatial and temporal regulatory mechanisms. Our efforts have focused on the FtsZ protein which assembles into a cytoskeletal ring that recruits other proteins to the division site. FtsZ is the ancestral homologue of eukaryotic tubulins and undergoes dynamic assembly during the cell cycle. It is the target of several endogenous inhibitors that participate in the regulation of cell division as part of the normal cell cycle or in response to DNA damage. Our recent work has shown that SulA and MinC are inhibitors of FtsZ assembly, however, they function quite differently. SulA is synthesized following DNA damage and sequesters FtsZ preventing it from assembling. In contrast, MinC is part of a sophisticated spatial regulatory system that oscillates between the poles of the cell to prevent FtsZ from assembling near the cell poles. In vitro, MinC can prevent FtsZ assembly and acts by destabilizing FtsZ filaments. In vivo MinC requires MinD to be a functional inhibitor. MinD activates MinC by recruiting it to the membrane and conferring upon it a high affinity for a septal component. Our studies have demonstrated that MinD binds to the membrane through a C-terminal amphipathic helix. We have also shown that MinE can displace MinC from a MinCD vesicle complex and stimulate the MinD ATPase releasing MinD from the vesicle. We have also shown that MinD can polymerize on vesicles causing tubulation. Our studies have also defined the sites on MinC involved in its binding to MinD and in its binding to the septum. In the present proposal we will use genetic and biochemical approaches to further define the interactions among the Min proteins and between the Min proteins and FtsZ that are necessary to regulate cell division. We will also use the knowledge gained from our study of the E. coil Min system to explore the Min system from B. subtilis and a Par protein.