Cited by 64Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersAdvanced Proteomics Techniques and Applications

Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases

Grant, Seth G.N., Marshall, Michael C., Page, Keri-Lee, Cumiskey, Mark A., Armstrong, J. Douglas·2005·Human Molecular Genetics

Abstract

Proteomic experiments have produced a draft profile of the overall molecular composition of the mammalian neuronal synapse. It appears that synapses have over 1000 protein components and the mapping of their interactions, organization and functions will lead to a global view of the role of synapses in physiology and disease. A major functional subcomponent of the synaptic machinery is a multiprotein complex of glutamate receptors and adhesion proteins with associated adaptor and signalling enzymes totally 185 proteins known as the N-methyl-d-aspartate receptor complex/MAGUK associated signalling complex (NRC/MASC). Here, we review the proteomic studies and functions of NRC/MASC and specifically report on the role of its component genes in human diseases. Using a systematic literature search protocol, we identified reports of mutations or polymorphisms in 47 genes associated with 183 disorders, of which 54 were nervous system disorders. A similar number of genes are important in mouse synaptic plasticity and behaviour, where the NRC/MASC acts as a signalling complex with multiple functions provided by its individual protein components and their interactions. The individual gene mutations suggest not only an important role for the NRC/MASC in human diseases but that these diseases may be functionally connected by their common link to the NRC/MASC. The NRC/MASC is a rich source of genetic variation and provides a platform for understanding relationships of disease phenotype amenable to systematic studies such as the Genes to Cognition research consortium (www.genes2cognition.org) that links human and mouse genetics with proteomic studies.

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Crossref · 10.1093/hmg/ddi330

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Authors
Grant, S. G. N., Marshall, M. C., Page, K.-L., Cumiskey, M. A., & Armstrong, J. D.
Affiliations
Wellcome Sanger Institute (GB)
Corresponding author
Grant, Seth G.N.
Venue
Human Molecular Genetics
Published
2005-10-15
Volume
14
Issue
suppl_2
Pages
R225-R234
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2131679574
Cited by
64
References
16
Citations by year
2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 5
FWCI
2.77
Type
journal article
Language
en
Open access
closed
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
glutamate receptors, synaptic adhesion proteins, genetic mutations, genetic polymorphism, neurological disorders, synaptic plasticity, mouse behavior
MeSH terms
Humans, Mutation, Nervous System Diseases, Polymorphism, Genetic, Synapses, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Proteomics, Macromolecular Substances, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins

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