The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane.
The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane.
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DOI：
10.1083/jcb.150.1.253
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发表时间：
2000-07-10
影响因子：
7.8
通讯作者：
Moerman, D G
中科院分区：
文献类型：
--
作者：
Rogalski, T M;Mullen, G P;Gilbert, M M;Williams, B D;Moerman, D G
秀丽隐杆线虫的unc-52、Pat -2、Pat -3和unc-112基因纯合突变的胚胎表现出类似的Pat表型。肌凝蛋白和肌动蛋白在这些突变体的体壁肌细胞中不能组织成肌节，致密体和m线成分不能组装。unc-52 (perlecan), pat-2 （α-整合素）和pat-3 （β-整合素）基因编码ECM或跨膜蛋白，这些蛋白存在于致密体和m系的细胞-基质粘附位点。本研究描述了unc-112基因产物的鉴定，unc-112是一种新型的膜相关细胞内蛋白，在细胞-基质粘附复合物中与整合素共定位。这个含有720个氨基酸的UNC-112蛋白与米格-2同源，米格-2是一种功能未知的人类蛋白。这两种蛋白与talin和FERM蛋白超家族成员共享同源区域。我们已经确定一个功能性的UNC-112::GFP融合蛋白与PAT-3/β-整合素在成人和胚胎的体壁肌肉中共定位。我们还确定，在PAT-3/β-整合素整合到基底膜后，需要UNC-112来组织它，而不需要UNC-52/perlecan在基底膜中组织它，也不需要DEB-1/vinculin与PAT-3/β-整合素定位。此外，UNC-112需要UNC-52/perlecan和PAT-3/β-整合素的存在才能定位到肌细胞膜，而不需要DEB-1/vinculin。
Embryos homozygous for mutations in the unc-52, pat-2, pat-3, and unc-112 genes of C. elegans exhibit a similar Pat phenotype. Myosin and actin are not organized into sarcomeres in the body wall muscle cells of these mutants, and dense body and M-line components fail to assemble. The unc-52 (perlecan), pat-2 (α-integrin), and pat-3 (β-integrin) genes encode ECM or transmembrane proteins found at the cell–matrix adhesion sites of both dense bodies and M-lines. This study describes the identification of the unc-112 gene product, a novel, membrane-associated, intracellular protein that colocalizes with integrin at cell–matrix adhesion complexes. The 720–amino acid UNC-112 protein is homologous to Mig-2, a human protein of unknown function. These two proteins share a region of homology with talin and members of the FERM superfamily of proteins. We have determined that a functional UNC-112::GFP fusion protein colocalizes with PAT-3/β-integrin in both adult and embryonic body wall muscle. We also have determined that UNC-112 is required to organize PAT-3/β-integrin after it is integrated into the basal cell membrane, but is not required to organize UNC-52/perlecan in the basement membrane, nor for DEB-1/vinculin to localize with PAT-3/β-integrin. Furthermore, UNC-112 requires the presence of UNC-52/perlecan and PAT-3/β-integrin, but not DEB-1/vinculin to become localized to the muscle cell membrane.