Bunch T A, Graner M W, Fessler L I, Fessler J H, Schneider K D, Kerschen A, Choy L P, Burgess B W, Brower D L
University of Arizona, Department of Molecular Biology, Tuscon, Arizona 85721, USA.
Development. 1998 May;125(9):1679-89. doi: 10.1242/dev.125.9.1679.
Tiggrin is a novel extracellular matrix ligand for the Drosophila PS2 integrins. We have used flanking P elements to generate a precise deletion of tiggrin. Most flies lacking tiggrin die as larvae or pupae. A few adults do emerge and these appear to be relatively normal, displaying only misshapen abdomens and a low frequency of wing defects. Examination of larvae shows that muscle connections, function and morphology are defective in tiggrin mutants. Muscle contraction waves that extend the length of the larvae are much slower in tiggrin mutants. Direct examination of bodywall muscles shows defects in muscle attachment sites, where tiggrin is specifically localized, and muscles appear thinner. Transgenes expressing tiggrin are capable of rescuing tiggrin mutant phenotypes. Transgenes expressing a mutant tiggrin, whose Arg-Gly-Asp (RGD) integrin recognition sequence has been mutated to Leu-Gly-Ala (LGA) show much reduced, but significant, rescuing ability. Cell spreading assays detect no interactions of this mutant tiggrin with PS2 integrins. Therefore, while the RGD sequence is critical for PS2 interactions and full activity in the whole fly, the mutant tiggrin retains some function(s) that are probably mediated by interactions with other ECM molecules or cell surface receptors
Tiggrin是果蝇PS2整合素的一种新型细胞外基质配体。我们利用侧翼P元件精确缺失了tiggrin。大多数缺乏tiggrin的果蝇在幼虫或蛹期死亡。少数成虫能够羽化，这些成虫看起来相对正常，仅表现出腹部畸形和低频率的翅膀缺陷。对幼虫的检查表明，tiggrin突变体的肌肉连接、功能和形态存在缺陷。在tiggrin突变体中，沿着幼虫身体长度延伸的肌肉收缩波要慢得多。对体壁肌肉的直接检查显示，在tiggrin特异性定位的肌肉附着位点存在缺陷，并且肌肉看起来更细。表达tiggrin的转基因能够挽救tiggrin突变体表型。表达突变型tiggrin的转基因，其精氨酸-甘氨酸-天冬氨酸（RGD）整合素识别序列已突变为亮氨酸-甘氨酸-丙氨酸（LGA），显示出挽救能力大大降低，但仍具有显著的挽救能力。细胞铺展试验未检测到这种突变型tiggrin与PS2整合素之间的相互作用。因此，虽然RGD序列对于PS2相互作用和整个果蝇中的完整活性至关重要，但突变型tiggrin保留了一些可能由与其他细胞外基质分子或细胞表面受体的相互作用介导的功能。
