Scheiblin David A, Gao Junyuan, Caplan Jeffrey L, Simirskii Vladimir N, Czymmek Kirk J, Mathias Richard T, Duncan Melinda K
Department of Biological Sciences, University of Delaware, Newark, DE 19716, United States.
Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York, NY 11794-8661, United States.
Int J Biochem Cell Biol. 2014 May;50:132-45. doi: 10.1016/j.biocel.2014.02.021. Epub 2014 Mar 4.
β1-Integrin is a heterodimeric transmembrane protein that has roles in both cell-extra-cellular matrix and cell-cell interactions. Conditional deletion of β1-integrin from all lens cells during embryonic development results in profound lens defects, however, it is less clear whether this reflects functions in the lens epithelium alone or whether this protein plays a role in lens fibers. Thus, a conditional approach was used to delete β1-integrin solely from the lens fiber cells. This deletion resulted in two distinct phenotypes with some lenses exhibiting cataracts while others were clear, albeit with refractive defects. Analysis of "clear" conditional knockout lenses revealed that they had profound defects in fiber cell morphology associated with the loss of the F-actin network. Physiological measurements found that the lens fiber cells had a twofold increase in gap junctional coupling, perhaps due to differential localization of connexins 46 and 50, as well as increased water permeability. This would presumably facilitate transport of ions and nutrients through the lens, and may partially explain how lenses with profound structural abnormalities can maintain transparency. In summary, β1-integrin plays a role in maintaining the cellular morphology and homeostasis of the lens fiber cells.
β1整合素是一种异二聚体跨膜蛋白,在细胞与细胞外基质以及细胞间相互作用中均发挥作用。在胚胎发育期间,从所有晶状体细胞中条件性缺失β1整合素会导致严重的晶状体缺陷,然而,目前尚不清楚这是否仅反映了其在晶状体上皮中的功能,还是该蛋白在晶状体纤维中也发挥作用。因此,采用了一种条件性方法仅从晶状体纤维细胞中删除β1整合素。这种缺失导致了两种不同的表型,一些晶状体出现白内障,而另一些则是透明的,尽管存在屈光缺陷。对“透明”的条件性敲除晶状体进行分析发现,它们在纤维细胞形态上存在严重缺陷,与F-肌动蛋白网络的丧失有关。生理学测量发现,晶状体纤维细胞的缝隙连接耦联增加了两倍,这可能是由于连接蛋白46和50的定位差异以及水通透性增加所致。这大概有助于离子和营养物质通过晶状体的运输,并且可能部分解释了结构严重异常的晶状体如何能够保持透明。总之,β1整合素在维持晶状体纤维细胞的细胞形态和内环境稳定中发挥作用。