αPS2 integrin-mediated muscle attachment in Drosophila requires the ECM protein thrombospondin

αPS2 integrin-mediated muscle attachment in Drosophila requires the ECM protein thrombospondin
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DOI:
10.1016/j.mod.2007.03.005
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发表时间:
2007-07-01
影响因子:
2.6
通讯作者:
Vorbrueggen, Gerd
Vorbrueggen, Gerd
中科院分区:
生物学4区
文献类型:
--
作者:
Chanana, Bhavna;Graf, Roland;Vorbrueggen, Gerd

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在果蝇胚胎发生期间,体细胞肌肉与表皮肌腱细胞的附着需要异二聚体PS整合素蛋白(α-和β-亚基)。α-亚基互补表达,肌腱细胞特异性或肌肉特异性,而β-整联蛋白亚基在两种组织中表达。β-整联蛋白突变导致严重的肌肉脱离表型,而α-亚整联蛋白突变具有较弱或仅幼虫肌肉脱离表型。此外,已知作为整联蛋白结合配偶体的细胞外基质(ECM)蛋白的突变仅具有相对弱的作用,表明存在适当肌肉附着所需的另外的整联蛋白结合ECM蛋白。在这里,我们报告说,果蝇基因血小板反应蛋白(tsp)的突变导致胚胎肌肉脱落。TSP在发育和成熟的表皮腱细胞中特异性表达。它最初在节边缘细胞(肌腱前体)中的表达受刺猬依赖性信号的控制,而tsp在分化的肌腱细胞中的表达依赖于stripe编码的转录因子。在缺乏tsp活性的情况下,肌肉模式形成的任何方面以及肌肉和肌腱细胞之间的初始接触或肌肉与肌肉的附着都不会受到影响。然而,当肌肉收缩发生在胚胎发育后期,肌肉从肌腱细胞分离。Tsp蛋白定位于肌肉附着的腱细胞ECNI。遗传相互作用研究表明,Tsp特异性地与α(PS2)整联蛋白相互作用,并且需要这种相互作用来承受肌腱细胞处的肌肉收缩力。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
During Drosophila embryogenesis, the attachment of somatic muscles to epidermal tendon cells requires heterodimeric PS-integrin proteins (alpha- and beta-subunits). The alpha-subunits are expressed complementarily, either tendon cell- or muscle-specific, whereas the beta-integrin subunit is expressed in both tissues. Mutations of beta-integrin cause a severe muscle detachment phenotype, whereas alpha-sububnit mutations have weaker or only larval muscle detachment phenotypes. Furthermore, mutations of extracellular matrix (ECM) proteins known to act as integrin binding partners have Comparatively weak effects only, suggesting the presence of additional integrin binding ECM proteins required for proper muscle attachment. Here, we report that mutations in the Drosophila gene thrombospondin (tsp) cause embryonic muscle detachment. tsp is specifically expressed in both developing and mature epidermal tendon cells. Its initial expression in segment border cells, the tendon precursors, is under the control of hedgehog-dependent signaling, whereas tsp expression in differentiated tendon cells depends on the transcription factor encoded by stripe. In the absence of tsp activity, no aspect of muscle pattern formation as well as the initial contact between muscle and tendon cells nor muscle-to-muscle attachments are affected. However, when muscle contractions occur during late embryogenesis, muscles detach from the tendon cells. The Tsp protein is localized to the tendon cell ECNI where muscles attach. Genetic interaction studies indicate that Tsp specifically interacts with the alpha(PS2) integrin and that this interaction is needed to withstand the forces of muscle contractions at the tendon cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.