Assembly and Placement of the Cell Division Ring

 描述(申请人提供)：细胞如何在胞质分裂过程中形成特定的细胞形状并分裂成两个是细胞生物学中的基本问题。机械力、膜、细胞骨架和细胞外环境等结构元素以及信号网络都有助于确定细胞的形状。在这里，我们研究了裂殖酵母胞质分裂和细胞极化的机械调节机制。这些是简单的杆状真核细胞，生长在细胞顶端，使用收缩环和隔膜进行内侧分裂。初步结果表明，肌动球蛋白收缩环的机械力有助于形成环和隔膜细胞壁，确保细胞质分裂有效完成。机械机制也塑造了圆形的细胞末端，并有助于细胞的极性。通过定量细胞生物学和分子遗传学，我们将阐明这些机械调控机制，并表征这些途径中的关键调控成分。这些研究对理解哺乳动物细胞中基于机械的调节和细胞形状控制具有广泛的影响，并与癌症和心脏病等人类疾病有关。我们的具体目标是1)确定收缩环在协调隔膜形成中的作用；2)确定肌动蛋白和其他环成分在收缩环中的动态和分布是如何调节的；3)确定基于机械的机制如何调节细胞的形状和细胞末端的极性通路。

 DESCRIPTION (provided by applicant): How cells form specific cell shapes and divide into two during cytokinesis are fundamental questions in cell biology. Mechanical forces, structural elements such as the membranes, cytoskeleton and the extracellular environment, and signaling networks all contribute to specify the shape of the cell. Here, we study mechanical-based regulatory mechanisms for cytokinesis and cell polarization in the fission yeast Schizosaccharomyces pombe. These are simple rod-shaped eukaryotic cells that grow at cell tips and divide medially using a contractile ring and septum. Preliminary results suggest that mechanical forces from the actomyosin contractile ring contribute to shaping the ring and septum cell wall, ensuring that cytokinesis completes efficiently. Mechanical mechanisms also shape the rounded cell ends and contribute to cell polarity. Through quantitative cell biology and molecular genetics, we will elucidate these mechanoregulatory mechanisms and characterize key regulatory components in these pathways. These studies have broad impact on understanding mechanical-based regulation and cell shape control in mammalian cells and are relevant to human diseases such as cancer and heart disease. Our specific aims are 1) to determine to role of the contractile ring in coordinating formation of the septum; 2) to determine how the dynamics and distribution of actin and other ring components are regulated in the contractile ring; 3) to determine how mechanical-based mechanisms regulate cell shape and polarity pathways at the ends of the cell.