MIT Libraries homeMIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

ß-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X

Author(s)
Auerbach, Benjamin D.; Lefkowitz, Robert J.; Stoppel, Laura Jane; Senter, Rebecca K; Preza, Anthony R.; Bear, Mark; ... Show more Show less
Thumbnail
DownloadStoppel-2017-beta-Arrestin2 Couples Metabotrop.pdf (1.387Mb)
PUBLISHER_CC

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/
Metadata
Show full item record
Abstract
Synaptic protein synthesis is essential for modification of the brain by experience and is aberrant in several genetically defined disorders, notably fragile X (FX), a heritable cause of autism and intellectual disability. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu[subscript 5]), yet how mGlu[subscript 5] couples to the intracellular signaling pathways that regulate mRNA translation is poorly understood. Here, we provide evidence that β-arrestin2 mediates mGlu[subscript 5]-stimulated protein synthesis in the hippocampus and show that genetic reduction of β-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr[superscript 1−/y] mouse model of FX. Importantly, reducing β-arrestin2 does not induce psychotomimetic activity associated with full mGlu[subscript 5] inhibitors and does not affect G[subscript q] signaling. Thus, in addition to identifying a key requirement for mGlu[subscript 5]-stimulated protein synthesis, these data suggest that β-arrestin2-biased negative modulators of mGlu[subscript 5] offer significant advantages over first-generation inhibitors for the treatment of FX and related disorders.
Date issued
2017-03
URI
http://hdl.handle.net/1721.1/110158
Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Journal
Cell Reports
Publisher
Elsevier
Citation
Stoppel, Laura J. et al. “ß-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X.” Cell Reports 18.12 (2017): 2807–2814.
Version: Final published version
ISSN
2211-1247

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries homeMIT Libraries logo

Find us on

Twitter Facebook Instagram YouTube RSS

MIT Libraries navigation

SearchHours & locationsBorrow & requestResearch supportAbout us
PrivacyPermissionsAccessibility
MIT
Massachusetts Institute of Technology
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.