The cavin proteins are essential for caveola biogenesis and function. Here, we identify a role for the muscle-specific component, Cavin4, in skeletal muscle T-tubule development by analyzing two vertebrate systems: mouse and zebrafish. In both models Cavin4 localized to T-tubules and loss of Cavin4 resulted in aberrant T-tubule maturation. In zebrafish, which possess duplicated cavin4 paralogs, Cavin4b was shown to directly interact with the T-tubule-associated BAR domain protein, Bin1. Loss of both Cavin4a and Cavin4b caused aberrant accumulation of interconnected caveolae within the T-tubules, a fragmented T-tubule network enriched in Caveolin-3, and an impaired Ca²⁺ response upon mechanical stimulation. We propose a role for Cavin4 in remodeling the T-tubule membrane early in development by recycling caveolar components from the T-tubule to the sarcolemma. This generates a stable T-tubule domain lacking caveolae that is essential for T-tubule function.

中文翻译：

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特定于肌肉的Cavin4与Bin1相互作用以促进骨骼肌发育中T管的形成和稳定性

cavin蛋白对于小窝生物发生和功能至关重要。在这里，我们通过分析两个脊椎动物系统：小鼠和斑马鱼，确定了肌肉特异性成分Cavin4在骨骼肌T小管发育中的作用。在这两个模型中，Cavin4均定位于T管，而Cavin4的缺失导致T管的异常成熟。在具有重复的cavin4旁系同源物的斑马鱼中，Cavin4b被证明与T管相关的BAR域蛋白Bin1直接相互作用。Cavin4a和Cavin4b的缺失都会导致相互连接的海绵状小管在T管中异常积累，碎片化的，富含Caveolin-3的T管网络以及受损​​的Ca ²⁺机械刺激后的反应。我们提出了Cavin4在通过将海绵状细胞成分从T-小管循环到肌膜的过程中，在发育早期改造T-小管膜中的作用。这会生成一个稳定的，缺少小孔的T管结构域，这对T管功能至关重要。