Dynamin-2 Regulates Postsynaptic Cytoskeleton Organization and the Maturation of Neuromuscular Junction

Abstract

The neuromuscular junction (NMJ) governs rapid and efficient neuronal communication with muscle cells, which relies on the proper activity of postsynaptic compartment specialized with unique membrane and actin-dependent cytoskeleton organization. However, the intrinsic mechanism in muscle cells that contributes to the development and maintenance of the elaborate NMJ morphology is unclear. In this study, we discover that the large GTPase, dynamin, best-known for catalyzing synaptic vesicle endocytosis at the presynaptic membrane, is also involved in postsynaptic morphogenesis. By using cultured mouse myotube, Drosophila, and in vitro reconstitution assay, we demonstrate that dynamin-2 (Dyn2) is enriched in the postsynaptic membrane of muscle cells and is involved in the maturation of neurotransmitter receptor clusters and the functional integrity of NMJ. During the early stage of NMJ development, Dyn2 functions as a molecular girdle to regulate synaptic podosome turnover and promote the maturation of postsynaptic apparatus. After the maturation, Dyn2 remains enriched at NMJ to maintain proper actin cytoskeleton organization and its electrophysiological function. The self-assembly, GTP hydrolysis ability and Y597 phosphorylation of Dyn2 determine its localization at podosome and the actin bundling activity. Together, our results uncover a new function of Dyn2 on cytoskeleton remodeling and organization at the postsynaptic membrane of NMJ.