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Ma2/d promotes myonuclear positioning and association with the sarcoplasmic reticulum

机译：MA2 / D促进神经核核定位和与肌肉网的关联

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摘要

The cytoplasm of striated myofibers contains a large number of membrane organelles, including sarcoplasmic reticulum (SR), T-tubules and the nuclear membrane. These organelles maintain a characteristic juxtaposition that appears to be essential for efficient inter-membranous exchange of RNA, proteins and ions. We found that the membrane-associated Muscle-specific alpha 2/delta (Ma2/d) subunit of the Ca2+ channel complex localizes to the SR and T-tubules, and accumulates at the myonuclear surfaces. Furthermore, Ma2/d mutant larval muscles exhibit nuclear positioning defects, disruption of the nuclear-SR juxtapositioning, as well as impaired larval locomotion. Ma2/d localization at the nuclear membrane depends on the proper function of the nesprin ortholog Msp300 and the BAR domain protein Amphiphysin (Amph). Importantly, live imaging of muscle contraction in intact Drosophila larvae indicated altered distribution of Sarco/Endoplamic Reticulum Ca2+-ATPase (SERCA) around the myonuclei of Ma2/d mutant larvae. Co-immunoprecipitation analysis supports association between Ma2/d and Amph, and indirectly with Msp300. We therefore suggest that Ma2/d, in association with Msp300 and Amph, mediates interactions between the SR and the nuclear membrane.
机译：纹状体肌纤维的细胞质含有大量膜细胞器，包括肌肉网（SR），T型管和核膜。这些细胞器维持特征并置，对于RNA，蛋白和离子的有效膜交换似乎是必不可少的。我们发现CA2 +通道复合物的膜相关肌肉特异性α2/δ（MA2 / D）亚基定位于Sr和T型小管，并在神经核表面上积累。此外，MA2 / D突变体幼虫肌肉呈现核定位缺陷，核对核对偏叠的破坏，以及幼虫运动受损。核膜的MA2 / D定位取决于Nesprin Ortholog MSP300和条形域蛋白两亲素（AMPH）的适当功能。重要的是，完整的果蝇幼虫的肌肉收缩的实时成像表明，在MA2 / D突变体幼虫的亚核周围的Sarco /元素网Ca2 + -AtPase（Serca）的分布改变。共免疫沉淀分析支持MA2 / D和AMPH之间的关联，间接与MSP300间接相关。因此，我们表明，与MSP300和AMPH相关的MA2 / D介导SR和核膜之间的相互作用。

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