Neuromuscular junctions (NMJs) govern rapid and efficient neuronal communication with muscle cells, which relies on the proper architecture of specialized postsynaptic compartments. However, the intrinsic mechanism in muscle cells contributing to elaborate NMJ development has been unclear. In this study, we reveal that the GTPase dynamin-2 (Dyn2), best-known for catalyzing synaptic vesicle endocytosis at the presynaptic membrane, is also involved in postsynaptic morphogenesis. We demonstrate that Dyn2 is enriched in the postsynaptic membrane of muscle cells and is involved in the maturation of neurotransmitter receptor clusters via its actin bundling ability. Dyn2 functions as a molecular girdle to regulate synaptic podosome turnover and promote morphogenesis of the postsynaptic apparatus. In Drosophila NMJs, Dyn2 is required to organize the postsynaptic actin cytoskeleton and to mediate its electrophysiological activities. Mechanistically, the actin binding, self-assembly, GTP hydrolysis ability, and Y597 phosphorylation of Dyn2 all regulate its actin bundling activity. Together, our study uncovers a role for Dyn2 in cytoskeleton remodeling and organization at the postsynaptic membrane of NMJs.

中文翻译：

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Dynamin-2调节突触足小体成熟以促进神经肌肉接头的发育

神经肌肉接头（NMJ）控制与肌肉细胞的快速有效神经元通信，这依赖于专门的突触后隔室的适当结构。但是，尚不清楚肌细胞中导致精细NMJ发育的内在机制。在这项研究中，我们揭示了最著名的GTPase dynamin-2（Dyn2）催化突触前膜上的突触小泡内吞作用，也参与了突触后的形态发生。我们证明Dyn2丰富在肌肉细胞的突触后膜，并通过其肌动蛋白捆绑能力参与神经递质受体簇的成熟。Dyn2充当分子带，以调节突触足小体周转并促进突触后装置的形态发生。在果蝇NMJ中，Dyn2需要组织突触后肌动蛋白细胞骨架并介导其电生理活动。从机理上讲，Dyn2的肌动蛋白结合，自组装，GTP水解能力和Y597磷酸化均调节其肌动蛋白束缚活性。总之，我们的研究揭示了Dyn2在NMJ突触后膜的细胞骨架重塑和组织中的作用。