LIM2 AND THE LENS CORE SYNCYTIUM

项目摘要/摘要 纤维细胞之间的细胞间通讯对晶状体内稳态至关重要，而且众所周知， 缝隙连接促进了小分子在相邻纤维细胞之间的扩散。然而，最近，我们 有证据表明，蛋白质等大分子也可以在纤维细胞之间扩散。这个 细胞间蛋白质扩散的管道可能是有限的细胞-细胞融合区域。核聚变的存在 晶状体核心中的细胞之间确保晶状体的中心区域起到合胞体的作用。这个 核心合胞体的生理意义尚不清楚。 LIM2是晶状体中含量第二丰富的整膜蛋白。它是克拉丁超级的一员- 并且在晶状体中具有假定的粘合功能。在初步实验中，Lim2基因座是 在小鼠中被插入突变破坏，导致Lim2的功能缺失。值得注意的是，在 LIM2缺失时，晶状体未形成合胞体。此外，LIM2-Null小鼠晶状体的激光分析 揭示了晶状体的内部折射特性受到了严重的干扰。这些观察结果 提示晶状体膜蛋白(LIM2)的表达、合胞组织和 晶状体中的屈光功能。 目前的应用将研究大分子在晶状体之间扩散的分子机制。 细胞，LIM2在晶状体合体形成中的作用，以及合胞之间的关系 组织和透镜的梯度折射率(GRIN)。 这些研究有望为以前未被怀疑的细胞间联系提供新的见解。 大分子的扩散和透镜的光学质量。这些信息将反过来影响我们对形象的看法 眼睛的形成和晶状体在光学训练中的作用。项目叙事 晶状体的作用是将光线急剧聚焦在视网膜上。这个应用程序将检查细胞间的 蛋白质在晶状体内的运动决定了它的光学质量。

PROJECT SUMMARY/ABSTRACT Intercellular communication between fiber cells is critical for lens homeostasis and it is well established that gap junctions facilitate the diffusion of small molecules between adjacent fiber cells. Recently, however, we have obtained evidence that large molecules such as proteins can also diffuse between fiber cells. The conduits for intercellular protein diffusion may be regions of limited cell-cell fusion. The presence of fusions between cells in the lens core ensures that the central region of the lens functions as a syncytium. The physiological significance of the core syncytium is not known. Lim2 is the second most abundant integral membrane protein in the lens. It is a member of the claudin super- family and has putative adhesive functions in the lens. In preliminary experiments, the Lim2 locus was disrupted in mice by insertional mutagenesis, resulting in a functional null for Lim2. Significantly, in the absence of Lim2, the lens syncytium did not form. Furthermore, laser analysis of Lim2-null mouse lenses revealed that the internal refractive properties of the lens were profoundly disturbed. These observations suggest a link between the expression of a lens membrane protein (Lim2), syncytial organization, and refractive function in the lens. The current application will examine the molecular mechanism by which macromolecules diffuse between lens cells, the role of Lim2 in the formation of the lens syncytium, and the relationship between syncytial organization and the lens gradient refractive index (GRIN). These studies are expected to provide novel insights into the previously unsuspected link between intercellular diffusion of macromolecules and lens optical quality. This information will, in turn, inform our view of image formation in the eye and the role of the lens in the optical train. PROJECT NARRATIVE The role of the lens is to focus light sharply on the retina. This application will examine how the intercellular movement of protein within the lens contributes to its optical quality.