Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
J Cell Biol. 2021 Dec 6;220(12). doi: 10.1083/jcb.201905065. Epub 2021 Oct 11.
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.
窖蛋白对于小窝的生物发生和功能至关重要。在这里，我们通过分析两种脊椎动物模型（鼠和斑马鱼），鉴定了肌特异性组成部分窖蛋白 4（Cavin4）在骨骼肌 T 小管发育中的作用。在这两种模型中，Cavin4 定位于 T 小管，而 Cavin4 的缺失导致 T 小管成熟异常。在具有重复的窖蛋白 4 同源物的斑马鱼中，Cavin4b 被证明可以直接与 T 小管相关的 BAR 结构域蛋白 Bin1 相互作用。Cavin4a 和 Cavin4b 的缺失导致 T 小管内异常积聚相互连接的小窝，富含窖蛋白-3 的 T 小管网络碎片化，以及机械刺激时 Ca2+反应受损。我们提出了 Cavin4 在发育早期通过从小窝向肌膜再循环小窝成分来重塑 T 小管膜的作用。这产生了一个缺乏小窝的稳定的 T 小管区域，对于 T 小管功能至关重要。
