Perng Ming-Der, Zhang Qingjiong, Quinlan Roy A
School of Biological and Biomedical Sciences, The University of Durham, DH1 3LE, UK.
Exp Cell Res. 2007 Jun 10;313(10):2180-8. doi: 10.1016/j.yexcr.2007.04.005. Epub 2007 Apr 6.
Filensin (BFSP1) and CP49 (BFSP2) represent two members of the IF protein superfamily that are thus far exclusively expressed in the eye lens. Mutations in both proteins cause lens cataract and careful consideration of the detail of these cataract phenotypes alerts us to several interesting features concerning the function of filensin (BFSP1) and CP49 (BFSP2) in the lens. With the first filensin (BFSP1) mutation now having been reported to cause a recessive cataract phenotype, there is the suggestion that the mutation could predispose heterozygote carriers to the early onset of age-related nuclear cataract. In the case of CP49 (BFSP2), there are now three unrelated families who have been identified with a common E233 Delta mutation. Very interestingly this is linked to myopia in one family. Despite the apparent phenotypic differences of the filensin (BFSP1) and CP49 (BFSP2) mutations, the data are still consistent with the beaded filament proteins being essential for lens function and specifically contributing to the optical properties of the lens. The fact that none of the mutations thus far reported affect either the conserved LNDR or TYRKLLEGE motifs that flank the central rod domain supports the view that this pair of IF proteins have unusual structural features and a distinctive assembly mechanism. The multiple sequence divergences suggest these proteins have been adapted to the specific functional requirements of lens fibre cells, a function that can be traced from squid to man.
丝纤蛋白（BFSP1）和CP49（BFSP2）是中间丝蛋白超家族的两个成员，迄今为止仅在晶状体中表达。这两种蛋白的突变都会导致晶状体白内障，仔细研究这些白内障表型的细节会让我们注意到一些关于丝纤蛋白（BFSP1）和CP49（BFSP2）在晶状体中功能的有趣特征。随着首个丝纤蛋白（BFSP1）突变被报道可导致隐性白内障表型，有人提出该突变可能使杂合子携带者易患早发性年龄相关性核性白内障。就CP49（BFSP2）而言，目前已在三个无亲缘关系的家族中发现了常见的E233缺失突变。非常有趣的是，在其中一个家族中这与近视有关。尽管丝纤蛋白（BFSP1）和CP49（BFSP2）突变的表型存在明显差异，但数据仍表明串珠状细丝蛋白对晶状体功能至关重要，且特别有助于晶状体的光学特性。目前报道的所有突变均未影响位于中央杆状结构域两侧的保守LNDR或TYRKLLEGE基序，这一事实支持了这对中间丝蛋白具有不同寻常的结构特征和独特组装机制的观点。多个序列差异表明这些蛋白已适应晶状体纤维细胞的特定功能需求，这种功能从鱿鱼到人类都能追溯到。
