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Neurotransmitters drive combinatorial multistate postsynaptic density networks

Coba, Marcelo P., Pocklington, Andrew ORCID:, Collins, Mark O., Kopanitsa, Maksym V., Uren, Rachel T., Swamy, Sajani, Croning, Mike D. R., Choudhary, Jyoti S. and Grant, Seth G. N. 2009. Neurotransmitters drive combinatorial multistate postsynaptic density networks. Science Signaling 2 (68) , ra19. 10.1126/scisignal.2000102

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The mammalian postsynaptic density (PSD) comprises a complex collection of ~1100 proteins. Despite extensive knowledge of individual proteins, the overall organization of the PSD is poorly understood. Here, we define maps of molecular circuitry within the PSD based on phosphorylation of postsynaptic proteins. Activation of a single neurotransmitter receptor, the N-methyl-D-aspartate receptor (NMDAR), changed the phosphorylation status of 127 proteins. Stimulation of ionotropic and metabotropic glutamate receptors and dopamine receptors activated overlapping networks with distinct combinatorial phosphorylation signatures. Using peptide array technology, we identified specific phosphorylation motifs and switching mechanisms responsible for the integration of neurotransmitter receptor pathways and their coordination of multiple substrates in these networks. These combinatorial networks confer high information-processing capacity and functional diversity on synapses, and their elucidation may provide new insights into disease mechanisms and new opportunities for drug discovery

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: American Association for the Advancement of Science
ISSN: 1937-9145
Last Modified: 21 Oct 2022 09:45

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