Abstract / Description of output
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 language | English |
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Pages (from-to) | 2348–2356 |
Number of pages | 9 |
Journal | Cell Reports |
Volume | 21 |
Issue number | 9 |
DOIs | |
Publication status | Published - 28 Nov 2017 |
Fingerprint
Dive into the research topics of 'Cellular and molecular anatomy of the human neuromuscular junction'. Together they form a unique fingerprint.Datasets
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NMJ-morph
Jones, R. (Creator) & Gillingwater, T. (Creator), Edinburgh DataShare, 27 Jan 2016
DOI: 10.7488/ds/1490
Dataset
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TMT generated proteomic identification and quantification of muscle and NMJ enriched fractions in mice and humans
Wishart, T. (Creator), Edinburgh DataShare, 25 Oct 2017
DOI: 10.7488/ds/2240
Dataset
Profiles
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Tom Gillingwater
- Deanery of Biomedical Sciences - Chair of Anatomy
- Centre for Discovery Brain Sciences
- Euan MacDonald Centre for Motor Neuron Disease Research
- Edinburgh Neuroscience
Person: Academic: Research Active
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Ross Jones
- Deanery of Biomedical Sciences - Senior Lecturer
- Centre for Discovery Brain Sciences
- Euan MacDonald Centre for Motor Neuron Disease Research
- Edinburgh Neuroscience - Lecturer in Clinical/Surgical Anatomy
Person: Academic: Research Active
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Martin Simmen
- Deanery of Biomedical Sciences - Senior Lecturer
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active