Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3

Martin Hruska; Nathan T Henderson; Nan L Xia; Sylvain J Le Marchand; Matthew B Dalva

doi:10.1038/nn.4140

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Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3

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Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3

Martin Hruska, Nathan T Henderson, Nan L Xia, Sylvain J Le Marchand and Matthew B Dalva

Nature neuroscience, v 18(11), pp 1594-1605

01 Nov 2015

DOI: https://doi.org/10.1038/nn.4140

PMID: 26479588

Featured in Collection : UN Sustainable Development Goals @ Drexel

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396457View

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Abstract

Animals

Cats

Disks Large Homolog 4 Protein

Ephrin-B3 - genetics

Ephrin-B3 - metabolism

Female

Guanylate Kinases - genetics

Guanylate Kinases - metabolism

Intracellular Signaling Peptides and Proteins - genetics

Intracellular Signaling Peptides and Proteins - metabolism

Male

Membrane Proteins - genetics

Membrane Proteins - metabolism

Neurons - metabolism

Protein Processing, Post-Translational - genetics

Rats

Receptors, AMPA - metabolism

Receptors, N-Methyl-D-Aspartate - metabolism

Synapses - metabolism

Pregnancy

Organization of signaling complexes at excitatory synapses by membrane-associated guanylate kinase (MAGUK) proteins regulates synapse development, plasticity, senescence and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches and in vivo models that the trans-synaptic organizing protein ephrin-B3 controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a newly identified mitogen-associated protein kinase (MAPK)-dependent phosphorylation site on ephrin-B3, Ser332. Unphosphorylated ephrin-B3 was enriched at synapses, and interacted directly with and stabilized PSD-95 at synapses. Activity-induced phosphorylation of Ser332 dispersed ephrin-B3 from synapses, prevented the interaction with PSD-95 and enhanced the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity.

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Title: Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3
Creators: Martin Hruska - Jefferson Hospital for Neuroscience
Nathan T Henderson - Jefferson Hospital for Neuroscience
Nan L Xia - Jefferson Hospital for Neuroscience
Sylvain J Le Marchand - Drexel University
Matthew B Dalva - Jefferson Hospital for Neuroscience
Publication Details: Nature neuroscience, v 18(11), pp 1594-1605
Publisher: Springer Nature
Number of pages: 12
Grant note: R01 DA022727 / NIDA NIH HHS R01 MH073357 / NIMH NIH HHS R01 MH086425 / NIMH NIH HHS MH100093 / NIMH NIH HHS R01 MH100093 / NIMH NIH HHS MH086425 / NIMH NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: Cell Imaging Center
Web of Science ID: WOS:000363830700017
Scopus ID: 2-s2.0-84945405591
Other Identifier: 991021892515504721

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Web of Science research areas: Neurosciences

Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3

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UN Sustainable Development Goals (SDGs)

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