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Cell Rep. 2017 Nov 28;21(9):2348-2356. doi: 10.1016/j.celrep.2017.11.008.

Cellular and Molecular Anatomy of the Human Neuromuscular Junction.

Author information

1
Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK; Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH8 9AG, UK.
2
Physics and Astronomy, University of Exeter, Exeter EX4 4QL, UK.
3
Neurobiology, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK.
4
Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK.
5
Fingerprints Proteomics, University of Dundee, Dundee DD1 5EH, UK.
6
Department of Orthopaedic Surgery, University of Edinburgh, Edinburgh EH16 4SB, UK.
7
Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH8 9AG, UK; Neurobiology, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK.
8
Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK; Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH8 9AG, UK. Electronic address: t.gillingwater@ed.ac.uk.

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.

KEYWORDS:

active zone; aging; comparative anatomy; human; mouse; nervous system; neuromuscular junction; proteomics; super-resolution imaging; synapse

PMID:
29186674
PMCID:
PMC5723673
DOI:
10.1016/j.celrep.2017.11.008
[Indexed for MEDLINE]
Free PMC Article

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