Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
J Cell Biol. 2012 Sep 3;198(5):833-46. doi: 10.1083/jcb.201204102. Epub 2012 Aug 27.
Striated muscle fibers are characterized by their tightly organized cytoplasm. Here, we show that the Drosophila melanogaster KASH proteins Klarsicht (Klar) and MSP-300 cooperate in promoting even myonuclear spacing by mediating a tight link between a newly discovered MSP-300 nuclear ring and a polarized network of astral microtubules (aMTs). In either klar or msp-300(ΔKASH), or in klar and msp-300 double heterozygous mutants, the MSP-300 nuclear ring and the aMTs retracted from the nuclear envelope, abrogating this even nuclear spacing. Anchoring of the myonuclei to the core acto-myosin fibrillar compartment was mediated exclusively by MSP-300. This protein was also essential for promoting even distribution of the mitochondria and ER within the muscle fiber. Larval locomotion is impaired in both msp-300 and klar mutants, and the klar mutants were rescued by muscle-specific expression of Klar. Thus, our results describe a novel mechanism of nuclear spacing in striated muscles controlled by the cooperative activity of MSP-300, Klar, and astral MTs, and demonstrate its physiological significance.
横纹肌纤维的特点是其细胞质排列紧密。在这里，我们表明，果蝇的 KASH 蛋白 Klarsicht (Klar) 和 MSP-300 通过介导新发现的 MSP-300 核环和极性星体微管 (aMTs) 之间的紧密联系，共同促进均匀的核间距。在 klar 或 msp-300(ΔKASH)缺失，或 klar 和 msp-300 双杂合突变体中，MSP-300 核环和 aMTs 从核膜缩回，破坏了这种均匀的核间距。肌核锚定到核心肌动球蛋白纤维状隔室是由 MSP-300 介导的。该蛋白对于促进线粒体和 ER 在肌肉纤维内的均匀分布也是必需的。msp-300 和 klar 突变体中的幼虫运动能力受损，klar 突变体通过肌肉特异性表达 Klar 得到挽救。因此，我们的结果描述了一种由 MSP-300、Klar 和星体 MTs 的协同活性控制的横纹肌核间距的新机制，并证明了其生理意义。
