LIM2 AND THE LENS CORE SYNCYTIUM

LIM2 和晶状体核心合胞体

• 批准号: 8323432
• 负责人: Steven Bassnett
• 金额: $ 36.12万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323432
• 关键词: Adhesives; Biological Process; Cell Membrane Proteins; Cell fusion; Cell membrane; Cells; Communication; Confocal Microscopy; Crystallins; Data; Diffuse; Diffusion; Ensure; Eye; Family; Gap Junctions; Giant Cells; Homeostasis; Image; Insertional Mutagenesis; Integral Membrane Protein; Knock-out; Knockout Mice; Lasers; Lens Fiber; Life; Light; Link; Location; Maps; Mediating; Membrane Proteins; Molecular; Movement; Mus; Nature; Optics; Pathway interactions; Performance; Phenotype; Physiological; Physiology; Play; Population; Property; Proteins; Publishing; Refractive Indices; Relative (related person); Retina; Role; Scanning; Shapes; System; Testing; Tissues; Training; Work; abstracting; base; cellular pathology; electric impedance; fiber cell; insight; intercellular communication; lens; macromolecule; member; mutant; novel; protein distribution; research study; small molecule

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.

项目总结/摘要 纤维细胞之间的细胞间通讯对于透镜内稳态是至关重要的，并且已经充分确定， 间隙连接促进小分子在相邻纤维细胞之间的扩散。然而，最近，我们 已经获得了大分子如蛋白质也可以在纤维细胞之间扩散的证据。的 用于细胞间蛋白质扩散的导管可以是有限的细胞-细胞融合区域。融合的存在 在透镜芯中的细胞之间的间隔确保了透镜的中心区域作为合胞体。的 核心合胞体的生理学意义尚不清楚。 Lim 2是透镜中第二丰富的整合膜蛋白。它是克劳丁超级- 并且在透镜中具有假定的粘合剂功能。在初步实验中， 通过插入诱变在小鼠中破坏，导致Lim 2的功能无效。值得注意的是，在 当Lim 2缺失时，透镜合胞体不形成。此外，Lim 2-null小鼠晶状体的激光分析 揭示了透镜的内部折射特性受到了严重的干扰。这些观察结果 表明透镜膜蛋白（Lim 2）的表达、合胞体组织和 透镜的折射功能。 当前的应用将研究大分子在透镜之间扩散的分子机制 细胞，Lim 2在透镜合胞体形成中的作用，以及合胞体之间的关系。 组织和透镜梯度折射率（GRIN）。 这些研究有望为以前未被怀疑的细胞间的联系提供新的见解。 大分子的扩散和透镜的光学质量。这些信息反过来又会影响我们对图像的看法 眼睛中的形成以及光学系统中透镜的作用。项目叙述 透镜的作用是把光线清晰地聚焦在视网膜上。这个应用程序将研究细胞间 蛋白质在透镜内的移动有助于其光学质量。