Abstract
SummaryThe 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.
Highlights
Synapses play fundamental roles in the form and function of the nervous system both in health and during disease
Many of the fundamental principles governing synaptic form and function in the nervous system were discovered from early experiments examining neuromuscular junction (NMJ) in model organisms (Slater, 2015)
Tissue samples were obtained from surgical discard material from twenty patients undergoing lower limb amputation for a variety of clinical indications, including complications of peripheral vascular disease (PVD) and nonPVD-related cases
Summary
Jones et al reveal fundamental differences between synapses in humans and lower mammals. They show that human neuromuscular junctions (NMJs) are smaller and more fragmented than comparable synapses from mice, with a distinct molecular composition. Human NMJs were remarkably stable across the entire adult lifespan. Highlights d Human neuromuscular junctions (NMJs) are morphologically distinct from rodent NMJs d Human NMJs are remarkably stable across the adult lifespan d Active zone proteins, including SNAP25, are differentially localized in human NMJs d Significant divergence between the synaptic proteome of human and mouse NMJs. Jones et al, 2017, Cell Reports 21, 2348–2356 November 28, 2017 a 2017 The Author(s).
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