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dc.contributor.authorScheefhals, N.
dc.contributor.authorCatsburg, L.A.E.
dc.contributor.authorBlanpied, T.A.
dc.date.accessioned2019-10-18T13:16:50Z
dc.date.available2019-10-18T13:16:50Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85073106741&doi=10.1016%2fj.celrep.2019.08.102&partnerID=40&md5=baec45fafea7278680cf189c90580eaa
dc.identifier.urihttp://hdl.handle.net/10713/11178
dc.description.abstractActivation of postsynaptic metabotropic glutamate receptors (mGluRs) modulates neuronal excitability and synaptic plasticity, while deregulation of mGluR signaling has been implicated in neurodevelopmental disorders. Overstimulation of mGluRs is restricted by the rapid endocytosis of receptors after activation. However, how membrane trafficking of mGluRs at synapses is controlled remains poorly defined. We find that in hippocampal neurons, the agonist-induced receptor internalization of synaptic mGluR5 is significantly reduced in Shank knockdown neurons. This is rescued by the re-expression of wild-type Shanks, but not by mutants unable to bind Homer1b/c, Dynamin2, or Cortactin. These effects are paralleled by a reduction in synapses associated with an endocytic zone. Moreover, a mutation in SHANK2 found in autism spectrum disorders (ASDs) similarly disrupts these processes. On the basis of these findings, we propose that synaptic Shank scaffolds anchor the endocytic machinery to govern the efficient trafficking of mGluR5 and to balance the surface expression of mGluRs to efficiently modulate neuronal functioning. Copyright 2019 The Author(s).en_US
dc.description.urihttps://doi.org/10.1016/j.celrep.2019.08.102en_US
dc.language.isoen_USen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofCell reports
dc.subjectendocytic zoneen_US
dc.subjectendocytosisen_US
dc.subjectmetabotropic glutamate receptoren_US
dc.subjectpostsynaptic densityen_US
dc.subjectreceptor traffickingen_US
dc.subjectShanken_US
dc.subjectsynaptic transmissionen_US
dc.titleShank Proteins Couple the Endocytic Zone to the Postsynaptic Density to Control Trafficking and Signaling of Metabotropic Glutamate Receptor 5en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.celrep.2019.08.102
dc.identifier.pmid31597090


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