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 (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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
Early online date28 Nov 2017
DOIs
Publication statusPublished - 28 Nov 2017

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Neuromuscular Junction
Anatomy
Imaging techniques
Neurons
Muscle
Animals
Proteins
Proteomics
Synapses
Motor Neurons
Skeletal Muscle
Animal Models

Keywords

  • Journal article
  • Human
  • Synapse
  • Neuromuscular junction
  • Aging
  • Active zone

Cite this

Jones, R. A., Harrison, C., Eaton, S. L., Llavero Hurtado, M., Graham, L. C., Alkhammash, L., ... Gillingwater, T. H. (2017). Cellular and Molecular Anatomy of the Human Neuromuscular Junction. Cell Reports, 21(9), 2348-2356. https://doi.org/10.1016/j.celrep.2017.11.008
Jones, Ross A. ; Harrison, Carl ; Eaton, Samantha L. ; Llavero Hurtado, Maica ; Graham, Laura C. ; Alkhammash, Leena ; Oladiran, Oladayo A. ; Gale, Andy ; Lamont, Douglas J. ; Simpson, Hamish ; Simmen, Martin W. ; Soeller, Christian ; Wishart, Thomas M. ; Gillingwater, Thomas H. / Cellular and Molecular Anatomy of the Human Neuromuscular Junction. In: Cell Reports. 2017 ; Vol. 21, No. 9. pp. 2348-2356.
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Jones, RA, Harrison, C, Eaton, SL, Llavero Hurtado, M, Graham, LC, Alkhammash, L, Oladiran, OA, Gale, A, Lamont, DJ, Simpson, H, Simmen, MW, Soeller, C, Wishart, TM & Gillingwater, TH 2017, 'Cellular and Molecular Anatomy of the Human Neuromuscular Junction', Cell Reports, vol. 21, no. 9, pp. 2348-2356. https://doi.org/10.1016/j.celrep.2017.11.008

Cellular and Molecular Anatomy of the Human Neuromuscular Junction. / Jones, Ross A.; Harrison, Carl; Eaton, Samantha L.; Llavero Hurtado, Maica; Graham, Laura C.; Alkhammash, Leena; Oladiran, Oladayo A.; Gale, Andy; Lamont, Douglas J.; Simpson, Hamish; Simmen, Martin W.; Soeller, Christian; Wishart, Thomas M.; Gillingwater, Thomas H. (Lead / Corresponding author).

In: Cell Reports, Vol. 21, No. 9, 28.11.2017, p. 2348-2356.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cellular and Molecular Anatomy of the Human Neuromuscular Junction

AU - Jones, Ross A.

AU - Harrison, Carl

AU - Eaton, Samantha L.

AU - Llavero Hurtado, Maica

AU - Graham, Laura C.

AU - Alkhammash, Leena

AU - Oladiran, Oladayo A.

AU - Gale, Andy

AU - Lamont, Douglas J.

AU - Simpson, Hamish

AU - Simmen, Martin W.

AU - Soeller, Christian

AU - Wishart, Thomas M.

AU - Gillingwater, Thomas H.

N1 - 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.).

PY - 2017/11/28

Y1 - 2017/11/28

N2 - 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.

AB - 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.

KW - Journal article

KW - Human

KW - Synapse

KW - Neuromuscular junction

KW - Aging

KW - Active zone

U2 - 10.1016/j.celrep.2017.11.008

DO - 10.1016/j.celrep.2017.11.008

M3 - Article

VL - 21

SP - 2348

EP - 2356

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 9

ER -

Jones RA, Harrison C, Eaton SL, Llavero Hurtado M, Graham LC, Alkhammash L et al. Cellular and Molecular Anatomy of the Human Neuromuscular Junction. Cell Reports. 2017 Nov 28;21(9):2348-2356. https://doi.org/10.1016/j.celrep.2017.11.008