Li X, Graner M W, Williams E L, Roote C E, Bunch T A, Zusman S
Department of Biology, University of Rochester, Rochester, New York 14627, USA.
Development. 1998 Feb;125(4):701-11. doi: 10.1242/dev.125.4.701.
The integrins are a family of transmembrane heterodimeric proteins that mediate adhesive interactions and participate in signaling across the plasma membrane. In this study we examine the functional significance of the cytoplasmic domains of the alphaPS1, alphaPS2 and betaPS subunits of the Drosophila Position Specific (PS) integrin family by analyzing the relationship between cytoplasmic domain structure and function in the context of a developing organism. By examining the ability of ssPS molecules lacking the cytoplasmic domain to rescue embryonic abnormalities associated with PS integrin loss, we find that although many embryonic events require the betaPS cytoplasmic domain, this portion of the molecule is not required for at least two processes requiring PS integrins: formation of midgut constrictions and maintaining germband integrity. Furthermore, our studies demonstrate that mutant proteins affecting four highly conserved amino acid residues in the cytoplasmic tail function with different efficiencies during embryonic development, suggesting that interaction of PS integrins with cytoplasmic ligands is developmentally modulated during embryogenesis. We have also examined the ability of alphaPS1 and alphaPS2 to function without their cytoplasmic domains. By analyzing the ability of transgenes producing truncated alphaPS molecules to rescue abnormalities associated with integrin loss, we find that the cytoplasmic tail of alphaPS2 is essential for both embryonic and postembryonic processes, while this portion of alphaPS1 is not required for function in the wing and in the retina. Furthermore, temperature-shift experiments suggest roles for the alphaPS2 cytoplasmic domain in signaling events occurring in the developing wing.
整合素是一类跨膜异二聚体蛋白家族，介导黏附相互作用并参与跨质膜的信号传导。在本研究中，我们通过分析果蝇位置特异性（PS）整合素家族的αPS1、αPS2和βPS亚基细胞质结构域在发育中的生物体背景下的结构与功能关系，来研究其功能意义。通过检测缺乏细胞质结构域的βPS分子拯救与PS整合素缺失相关的胚胎异常的能力，我们发现尽管许多胚胎事件需要βPS细胞质结构域，但至少有两个需要PS整合素的过程不需要该分子的这一部分：中肠收缩的形成和维持胚带完整性。此外，我们的研究表明，影响细胞质尾部四个高度保守氨基酸残基的突变蛋白在胚胎发育过程中具有不同的功能效率，这表明PS整合素与细胞质配体的相互作用在胚胎发生过程中受到发育调控。我们还检测了αPS1和αPS2在没有其细胞质结构域的情况下发挥功能的能力。通过分析产生截短αPS分子的转基因拯救与整合素缺失相关异常的能力，我们发现αPS2的细胞质尾部对于胚胎和胚胎后过程都是必不可少的，而αPS1的这一部分在翅膀和视网膜的功能中则不需要。此外，温度转换实验表明αPS2细胞质结构域在发育中的翅膀中发生的信号事件中发挥作用。
