Slowdown promotes muscle integrity by modulating integrin-mediated adhesion at the myotendinous junction
Slowdown promotes muscle integrity by modulating integrin-mediated adhesion at the myotendinous junction
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DOI：
10.1242/dev.043703
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发表时间：
2010-03-01
期刊：
影响因子：
4.6
通讯作者：
Volk, Talila
中科院分区：
文献类型：
--
作者：
Gilsohn, Eliezer;Volk, Talila
肌腱接头 (MTJ) 的正确组装对于正常的肌肉功能至关重要。在果蝇中，该连接点包括半粘附连接点，这些连接点是在肌肉到达其相应的腱细胞时形成的。 MTJ主要包括肌肉特异性αPS2βPS整合素受体及其腱源性细胞外基质配体血小板反应蛋白（Tsp）。我们报告了一种名为 Slowdown (Slow) 的新型肌腱衍生分泌蛋白的鉴定和功能分析。纯合慢突变幼虫表现出肌肉或肌腱断裂，幼虫运动缓慢，部分致死，幸存的成蝇无法飞行。这些缺陷是由于胚胎 MTJ 组装不当造成的。在慢突变体中，Tsp 过早地积聚在肌肉末端，肌肉前缘的形态发生变化，MTJ 结构发生异常。 Slow被发现与Tsp形成蛋白质复合物。该复合物具有生物活性，能够改变肌肉末端的形态和方向性。我们的分析表明 Slow 是 MTJ 的重要组成部分，对于确保幼虫运动过程中肌肉和肌腱的完整性至关重要。
The correct assembly of the myotendinous junction (MTJ) is crucial for proper muscle function. In Drosophila, this junction comprises hemi-adherens junctions that are formed upon arrival of muscles at their corresponding tendon cells. The MTJ mainly comprises muscle-specific alpha PS2 beta PS integrin receptors and their tendon-derived extracellular matrix ligand Thrombospondin (Tsp). We report the identification and functional analysis of a novel tendon-derived secreted protein named Slowdown (Slow). Homozygous slow mutant larvae exhibit muscle or tendon rupture, sluggish larval movement, partial lethality, and the surviving adult flies are unable to fly. These defects result from improper assembly of the embryonic MTJ. In slow mutants, Tsp prematurely accumulates at muscle ends, the morphology of the muscle leading edge changes and the MTJ architecture is aberrant. Slow was found to form a protein complex with Tsp. This complex is biologically active and capable of altering the morphology and directionality of muscle ends. Our analysis implicates Slow as an essential component of the MTJ, crucial for ensuring muscle and tendon integrity during larval locomotion.