Cellular and molecular anatomy of the human neuromuscular junction

Ross A. Jones, Carl Harrison, Samantha L. Eaton, Maica Llavero Hurtado, Laura C. Graham, Leena Alkhammash, Oladayo A. Oladiran, Andy Gale, Douglas J. Lamont, Hamish Simpson, Martin W. Simmen, Christian Soeller, Thomas M. Wishart, Thomas H. Gillingwater

Research output: Contribution to journalArticlepeer-review

Abstract

The neuromuscular junction (NMJ) plays a fundamental role in transferring information from lower motor neuron to skeletal muscle to generate movement. It is also an experimentally accessible model synapse routinely studied in animal models to explore fundamental aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, and proteomic profiling to reveal the detailed cellular and molecular architecture of the human NMJ. Human NMJs were significantly smaller, less complex, and more fragmented than mouse NMJs. In contrast to mice, human NMJs were also remarkably stable across the entire adult lifespan, showing no signs of age-related degeneration or remodeling. Super-resolution imaging and proteomic profiling revealed distinctive distribution of active zone proteins and differential expression of core synaptic proteins and molecular pathways at the human NMJ. Taken together, these findings reveal human-specific cellular and molecular features of the NMJ that distinguish them from comparable synapses in other mammalian species.
Original languageEnglish
Pages (from-to)2348–2356
Number of pages9
JournalCell Reports
Volume21
Issue number9
DOIs
Publication statusPublished - 28 Nov 2017

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