Extracellular Phosphorylation of a Receptor Tyrosine Kinase Controls Synaptic Localization of NMDA Receptors and Regulates Pathological Pain

Simple item page
dc.contributor.authorHanamura, Kenjien_US
dc.contributor.authorWashburn, Halley R.en_US
dc.contributor.authorSheffler-Collins, Sean I.en_US
dc.contributor.authorXia, Nan L.en_US
dc.contributor.authorHenderson, Nathanen_US
dc.contributor.authorTillu, Dipti V.en_US
dc.contributor.authorHassler, Shayneen_US
dc.contributor.authorSpellman, Daniel S.en_US
dc.contributor.authorZhang, Guoanen_US
dc.contributor.authorNeubert, Thomas A.en_US
dc.contributor.authorPrice, Theodore J.en_US
dc.contributor.authorDalva, Matthew B.en_US
dc.contributor.utdAuthorHassler, Shayneen_US
dc.contributor.utdAuthorPrice, Theodore J.en_US
dc.date.accessioned2018-08-20T16:25:01Z
dc.date.available2018-08-20T16:25:01Z
dc.date.created2017-07
dc.descriptionIncludes supplementary materialen_US
dc.description.abstractExtracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2. Ligand-dependent Y504 phosphorylation modulates the EphB-NMDAR interaction in cortical and spinal cord neurons. Furthermore, Y504 phosphorylation enhances NMDAR localization and injury-induced pain behavior. By mediating inducible extracellular interactions that are capable of modulating animal behavior, extracellular tyrosine phosphorylation of EphBs may represent a previously unknown class of mechanism mediating protein interaction and function.en_US
dc.description.departmentSchool of Behavioral and Brain Sciencesen_US
dc.description.sponsorshipNational Institute of Mental Health (grant number MH100093). National Institute of General Medicine (grant number GM102575). National Center for Research Resources (grant number RR027990). National Institute on Drug Abuse (grant number DA022727). National Eye Institute Vision Training Grant (grant number EY007035). National Institute of Neurological Disorders and Stroke (grant number NS050276). National Institute of Neurological Disorders and Stroke (grant number NS065926).en_US
dc.identifier.bibliographicCitationHanamura, Kenji, Halley R. Washburn, Sean I. Sheffler-Collins, Nan L. Xia, et al. 2017. "Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain." PLOS Biology 15(7), doi:10.1371/journal.pbio.2002457en_US
dc.identifier.issn1545-7885en_US
dc.identifier.issue7en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/5989
dc.identifier.volume15en_US
dc.language.isoenen_US
dc.relation.urihttp://dx.doi.org/10.1371/journal.pbio.2002457en_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.source.journalPLOS Biologyen_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectBones—Canceren_US
dc.subjectReceptors, N-Methyl-D-Aspartateen_US
dc.subjectPosterior Horn Cellsen_US
dc.subjectReceptors, Eph Familyen_US
dc.subjectNeuralgiaen_US
dc.subjectReceptors, Purinergic P2Xen_US
dc.subjectVesicular Glutamate Transport Proteinsen_US
dc.titleExtracellular Phosphorylation of a Receptor Tyrosine Kinase Controls Synaptic Localization of NMDA Receptors and Regulates Pathological Painen_US
dc.typeTexten_US
dc.type.genrearticleen_US

Files

Original bundle

Now showing 1 - 2 of 2
Thumbnail Image
Name:
BBS-4097-8119.49.pdf
Size:
11.35 MB
Format:
Adobe Portable Document Format
Description:
Article
Download
No Thumbnail Available
Name:
BBS-4097-8119.49_S1.zip
Size:
4.78 MB
Format:
Unknown data format
Description:
Supplement files
Download

Collections

Price, Theodore J.