Cellular and Molecular Anatomy of the Human Neuromuscular Junction
Llavero Hurtado, M
Elsevier (Cell Press)
© 2017 The Author(s). Open Access funded by Biotechnology and Biological Sciences Research Council. Under a Creative Commons license: https://creativecommons.org/licenses/by/4.0/
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.
This work was supported by small project grant funding from Biomedical Sciences (Anatomy) at the University of Edinburgh (T.H.G. and R.A.J.), the Darwin Trust of Edinburgh (M.L.H.), and the BBSRC (Institute Strategic Programme Funding; T.M.W., S.L.E., and L.C.G.).
This is the final version of the article. Available from Elsevier via the DOI in this record.
Vol. 21 (9), pp. 2348 - 2356
Place of publication