Clathrin function directly derives from its coat structure, and while endocytosis is mediated by clathrin-coated pits, large plaques contribute to cell adhesion. Here, we show that the alternative splicing of a single exon of the clathrin heavy chain gene (CLTC exon 31) helps determine the clathrin coat organization. Direct genetic control was demonstrated by forced CLTC exon 31 skipping in muscle cells that reverses the plasma membrane content from clathrin plaques to pits and by promoting exon inclusion that stimulated flat plaque assembly. Interestingly, mis-splicing of CLTC exon 31 found in the severe congenital form of myotonic dystrophy was associated with reduced plaques in patient myotubes. Moreover, forced exclusion of this exon in WT mice muscle induced structural disorganization and reduced force, highlighting the contribution of this splicing event for the maintenance of tissue homeostasis. This genetic control on clathrin assembly should influence the way we consider how plasticity in clathrin-coated structures is involved in muscle development and maintenance.

中文翻译：

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网格蛋白重链的选择性剪接有助于从涂层凹坑到斑块的转变

网格蛋白的功能直接源自其外壳结构，虽然内吞作用是由网格蛋白包被的凹坑介导的，但大斑块有助于细胞粘附。在这里，我们证明网格蛋白重链基因的单个外显子（CLTC 外显子 31）的选择性剪接有助于确定网格蛋白外壳的组织。通过强制 CLTC 外显子 31 在肌肉细胞中跳跃，将质膜内容从网格蛋白斑块逆转为凹坑，并通过促进外显子包含刺激平坦斑块组装，证明了直接遗传控制。有趣的是，在严重先天性强直性肌营养不良症中发现的 CLTC 外显子 31 的错误剪接与患者肌管中斑块的减少有关。此外，在WT小鼠肌肉中强制排除该外显子会导致结构紊乱和力量减少，突出了该剪接事件对维持组织稳态的贡献。这种对网格蛋白组装的遗传控制应该会影响我们考虑网格蛋白涂层结构的可塑性如何参与肌肉发育和维持的方式。