Tubb B E, Bardien-Kruger S, Kashork C D, Shaffer L G, Ramagli L S, Xu J, Siciliano M J, Bryan J
Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.
Genomics. 2000 Apr 15;65(2):146-56. doi: 10.1006/geno.2000.6156.
Retinal fascin is a newly identified photoreceptor-specific paralog of the actin-bundling protein fascin. Fascins crosslink f-actin into highly ordered bundles within dynamic cell extensions such as neuronal growth cone filopodia. We have isolated cDNA and genomic clones of human retinal fascin and characterized the structure of the human retinal fascin gene (FSCN2). The cDNA predicts a protein of 492 amino acids and molecular mass 55,057 that shows 94% identity to bovine retinal fascin and 56% identity to human fascin. Promoter analysis reveals a consensus retinoic acid response element and several potential binding sites for transcription factors Crx and Nrl, which correlates with the retina-specific expression of FSCN2 mRNA. Fluorescence in situ hybridization analysis and genomic clone sequencing indicate that the FSCN2 gene lies within 200 kb of the actin gene ACTG1 at 17q25. Database searches revealed that the human fascin gene FSCN1 and actin gene ACTB at 7p22 also coexist within a 200-kb genomic clone. The close physical linkage of these fascin/actin gene pairs suggests that they derive from a common gene duplication event and allows comparison of fascin and actin phylogenetic analyses. Finally, a possible link to the retinitis pigmentosa 17 allele (RP17) at distal 17q was excluded by demonstration of multiple independent segregation events in two RP17 kindreds. Informative FSCN2 polymorphisms were identified and will serve as useful markers in future linkage studies. The likely function of retinal fascin, in light of known fascin roles in other cell types, is to assemble actin microfilaments in support of photoreceptor disk morphogenesis.
视网膜丝束蛋白是一种新发现的肌动蛋白捆绑蛋白丝束蛋白的光感受器特异性旁系同源物。丝束蛋白将丝状肌动蛋白交联成动态细胞突起（如神经元生长锥丝状伪足）内的高度有序束状结构。我们分离出了人类视网膜丝束蛋白的cDNA和基因组克隆，并对人类视网膜丝束蛋白基因（FSCN2）的结构进行了表征。该cDNA预测编码一个由492个氨基酸组成、分子量为55,057的蛋白质，其与牛视网膜丝束蛋白的同一性为94%，与人类丝束蛋白的同一性为56%。启动子分析揭示了一个共有维甲酸反应元件以及转录因子Crx和Nrl的几个潜在结合位点，这与FSCN2 mRNA的视网膜特异性表达相关。荧光原位杂交分析和基因组克隆测序表明，FSCN2基因位于17q25处的肌动蛋白基因ACTG1的200 kb范围内。数据库搜索显示，7p22处的人类丝束蛋白基因FSCN1和肌动蛋白基因ACTB也共存于一个200 kb的基因组克隆中。这些丝束蛋白/肌动蛋白基因对的紧密物理连锁表明它们源自一个共同的基因复制事件，并允许对丝束蛋白和肌动蛋白的系统发育分析进行比较。最后，通过在两个RP17家族中证明多个独立的分离事件，排除了与17q远端的视网膜色素变性17等位基因（RP17）的可能联系。已鉴定出信息丰富的FSCN2多态性，它们将作为未来连锁研究中的有用标记。鉴于丝束蛋白在其他细胞类型中的已知作用，视网膜丝束蛋白的可能功能是组装肌动蛋白微丝以支持光感受器盘的形态发生。
