Dynamin-2 Regulates Postsynaptic Cytoskeleton Organization and Neuromuscular Junction Development
Journal
Cell reports
Journal Volume
33
Journal Issue
4
Date Issued
2020
Author(s)
Lin, Shan-Shan
Hsieh, Tsung-Lin
Liou, Gunn-Guang
Li, Tsai-Ning
Lin, Hsin-Chieh
Chang, Chiung-Wen
Wu, Hsiang-Yi
Yao, Chi-Kuang
Abstract
Neuromuscular junctions (NMJs) govern efficient neuronal communication with muscle cells, relying on proper architecture of specialized postsynaptic compartments. However, the intrinsic mechanism in muscle cells contributing to NMJ development remains unclear. In this study, we reveal that dynamin-2 (Dyn2) is involved in postsynaptic development of NMJs. Mutations of Dyn2 have been linked to human muscular disorder and centronuclear myopathy (CNM), as well as featured with muscle atrophy and defective NMJs, yet the function of Dyn2 at the postsynaptic membrane is largely unknown. We demonstrate that Dyn2 is enriched at the postsynaptic membrane and regulates NMJ development via actin remodeling. Dyn2 functions as an actin-bundling GTPase to regulate podosome turnover and cytoskeletal organization of the postsynaptic apparatus, and CNM-Dyn2 mutations display abnormal actin remodeling and electrophysiological activity of fly NMJs. Altogether, Dyn2 primarily regulates actin cytoskeleton remodeling and NMJ morphogenesis at the postsynaptic membrane, which is distinct from its endocytosis regulatory role at the presynaptic membrane.
Subjects
NMJ morphogenesis; actin-bundling protein; centronuclear myopathy; phosphorylation of Dyn2(Y597); podosome turnover; postsynaptic actin
SDGs
Other Subjects
actin; dynamin II; guanosine triphosphatase; DNM2 protein, human; dynamin II; Article; cell activity; cell maturation; cell membrane; centronuclear myopathy; controlled study; human; membrane electrophysiology; muscle atrophy; muscle disease; neuromuscular junction; postsynaptic membrane; priority journal; protein function; protein phosphorylation; cytoskeleton; growth, development and aging; metabolism; neuromuscular junction; physiology; Cytoskeleton; Dynamin II; Humans; Neuromuscular Junction
Type
journal article