Kao Gautam, Huang Cheng-chen, Hedgecock Edward M, Hall David H, Wadsworth William G
Department of Pathology, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Dev Biol. 2006 Feb 1;290(1):211-9. doi: 10.1016/j.ydbio.2005.11.026. Epub 2005 Dec 27.
Laminins are components of basement membranes that are required for morphogenesis, organizing cell adhesions and cell signaling. Studies have suggested that laminins function as alpha(x) beta(y) gamma(z) heterotrimers in vivo. In C. elegans, there is only one laminin beta gene, suggesting that it is required for all laminin functions. Our analysis is consistent with the role of the laminin beta as a subunit of laminin heterotrimers; the same cells express the laminin alpha, beta, and gamma subunits, the laminin beta subunit localizes to all basement membranes throughout development, and secretion of the beta subunit requires an alpha subunit. RNAi inhibition of the beta subunit gene or of the other subunit genes causes an embryonic lethality phenotype. Furthermore, a distinctive set of phenotypes is caused by both viable laminin alpha and beta partial loss-of-function mutations. These results show developmental roles for the laminin beta subunit, and they provide further genetic evidence for the importance of heterotrimer assembly in vivo.
层粘连蛋白是基底膜的组成成分，在形态发生、组织细胞黏附和细胞信号传导中发挥作用。研究表明，层粘连蛋白在体内以α(x)β(y)γ(z)异源三聚体的形式发挥功能。在秀丽隐杆线虫中，只有一个层粘连蛋白β基因，这表明它是所有层粘连蛋白功能所必需的。我们的分析与层粘连蛋白β作为层粘连蛋白异源三聚体亚基的作用一致；相同的细胞表达层粘连蛋白α、β和γ亚基，层粘连蛋白β亚基在整个发育过程中定位于所有基底膜，并且β亚基的分泌需要α亚基。RNA干扰抑制β亚基基因或其他亚基基因会导致胚胎致死表型。此外，一组独特的表型是由存活的层粘连蛋白α和β部分功能丧失突变引起的。这些结果显示了层粘连蛋白β亚基的发育作用，并为体内异源三聚体组装的重要性提供了进一步的遗传学证据。
