Misener V L, Hui C, Malapitan I A, Ittel M E, Joyner A L, Jongstra J
Arthritis Centre-Research Unit, Toronto Hospital Research Institute, University of Toronto, Ontario, Canada.
J Cell Sci. 1994 Dec;107 ( Pt 12):3591-600. doi: 10.1242/jcs.107.12.3591.
Mouse LSP1 is a 330 amino acid intracellular F-actin binding protein expressed in lymphocytes and macrophages but not in non-hematopoietic tissues. A 328 amino acid LSP1-related protein, designated S37, is expressed in murine bone marrow stromal cells, in fibroblasts, and in a myocyte cell line. The two proteins differ only at their N termini, the first 23 amino acid residues of LSP1 being replaced by 21 different residues in S37. The presence of different amino termini suggests that the LSP1 and S37 proteins are encoded by transcripts arising through alternative exon splicing. Here we report the genomic organization of the Lsp1 gene and show that the distinct N termini of LSP1 and S37 are encoded by two alternatively used exons, each containing a translational start codon. We also demonstrate that alternative 3' acceptor sites are used in the splicing of exon 5. This results in LSP1 and S37 transcripts that either do or do not contain 18 bp encoding the 6 amino acids HLIRHQ of the acidic domain. Therefore, the Lsp1 gene encodes four protein isoforms: full-length LSP1 and S37 proteins, designated LSP1-I and S37-I and the same proteins without the HLIRHQ sequence, designated LSP1-II and S37-II. By in situ hybridization analysis we show that the S37 isoforms are expressed in mesenchymal tissue, but not in adjacent epithelial tissue, of several developing organs during mouse embryogenesis. This, together with our finding that S37 is an F-actin binding protein, suggests that S37 is a cytoskeletal protein of mesenchymal cells, which may play a role in mesenchyme-induced epithelial differentiation during organogenesis.
小鼠LSP1是一种由330个氨基酸组成的细胞内F-肌动蛋白结合蛋白，在淋巴细胞和巨噬细胞中表达，但在非造血组织中不表达。一种由328个氨基酸组成的与LSP1相关的蛋白，命名为S37，在小鼠骨髓基质细胞、成纤维细胞和一种心肌细胞系中表达。这两种蛋白仅在其N端不同，LSP1的前23个氨基酸残基被S37中的21个不同残基取代。不同的N端的存在表明LSP1和S37蛋白是由通过选择性外显子剪接产生的转录本编码的。在这里，我们报告了Lsp1基因的基因组结构，并表明LSP1和S37不同的N端由两个交替使用的外显子编码，每个外显子都包含一个翻译起始密码子。我们还证明在第5外显子的剪接中使用了不同的3' 受体位点。这导致LSP1和S37转录本要么包含要么不包含编码酸性结构域6个氨基酸HLIRHQ的18 bp。因此，Lsp1基因编码四种蛋白质异构体：全长LSP1和S37蛋白，分别命名为LSP1-I和S37-I，以及不含HLIRHQ序列的相同蛋白，命名为LSP1-II和S37-II。通过原位杂交分析，我们表明在小鼠胚胎发育过程中，S37异构体在几个发育器官的间充质组织中表达，但在相邻的上皮组织中不表达。这与我们发现S37是一种F-肌动蛋白结合蛋白一起，表明S37是间充质细胞的一种细胞骨架蛋白，它可能在器官发生过程中间充质诱导的上皮分化中发挥作用。
