Zusman S, Grinblat Y, Yee G, Kafatos F C, Hynes R O
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.
Development. 1993 Jul;118(3):737-50. doi: 10.1242/dev.118.3.737.
The Drosophila position-specific (PS) antigens are homologues of the vertebrate integrins, a family of transmembrane proteins that function in cell-matrix and cell-cell adhesion. The common beta subunit of PS integrins (PS beta) is encoded by the lethal(l)myospheroid gene (mys) and is required during wing, eye and muscle development. By expressing PS beta protein at defined developmental periods, we have shown that PS integrins are required throughout pupation, but not earlier, for normal development of wings. In contrast, the key requirement for PS integrins in eye development occurs only in the late pupa. Furthermore, PS integrins are apparently not required for the differentiation of the ommatidial cells; only for their organization. These results are consistent with roles for PS integrins in the interactions between the wing epithelia during the two phases of pupal wing expansion and in maintaining the attachment of a fully formed fenestrated membrane to the basement membrane of the retina. We have also examined the functional significance of alternative splicing of the transcript of the mys gene using P element-mediated transformation to introduce transgenes producing only one of the two spliced forms of PS beta. We find that either form is sufficient to rescue postembryonic mys phenotypes in the wing, eye and muscle but that both of the two splice forms are necessary to rescue the mys embryonic defects. This result indicates a requirement for the alternative splicing of mys during embryogenesis. The location of the alternative exons suggests that the two forms of the PS beta integrin subunit may interact with alternative alpha subunits and/or ligands.
果蝇位置特异性(PS)抗原是脊椎动物整合素的同源物,整合素是一族跨膜蛋白,在细胞与基质以及细胞与细胞的黏附中发挥作用。PS整合素的常见β亚基(PSβ)由致死(l)肌球体基因(mys)编码,在翅、眼和肌肉发育过程中是必需的。通过在特定发育时期表达PSβ蛋白,我们发现PS整合素在整个化蛹过程中对翅的正常发育是必需的,但在更早阶段则不是。相反,PS整合素在眼发育中的关键需求仅出现在蛹后期。此外,PS整合素显然对小眼细胞的分化不是必需的;仅对它们的组织是必需的。这些结果与PS整合素在蛹期翅扩展的两个阶段中翅上皮细胞之间的相互作用以及维持完全形成的有孔膜与视网膜基底膜的附着中的作用一致。我们还利用P因子介导的转化来引入仅产生PSβ两种剪接形式之一的转基因,研究了mys基因转录本可变剪接的功能意义。我们发现任何一种形式都足以挽救翅、眼和肌肉中的胚胎后mys表型,但两种剪接形式对于挽救mys胚胎缺陷都是必需的。这一结果表明在胚胎发生过程中mys需要进行可变剪接。可变外显子的位置表明PSβ整合素亚基的两种形式可能与不同的α亚基和/或配体相互作用。