Rapid Synthesis of the X-Linked Mental Retardation Protein OPHN1 Mediates mGluR-Dependent LTD through Interaction with the Endocytic Machinery

Nadif Kasri, N., Nakano-Kobayashi, A., Van Aelst, L. (October 2011) Rapid Synthesis of the X-Linked Mental Retardation Protein OPHN1 Mediates mGluR-Dependent LTD through Interaction with the Endocytic Machinery. Neuron, 72 (2). pp. 300-315. ISSN 1097-4199 (Electronic)0896-6273 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22017989
DOI: 10.1016/j.neuron.2011.09.001

Abstract

Activation of group I metabotropic glutamate receptors leads to long-term depression (mGluR-LTD). Alterations in this form of plasticity have been linked to drug addiction and cognitive disorders. A key characteristic of mGluR-LTD is its dependence on rapid protein synthesis; however, the identities of the proteins mediating LTD remain elusive. Here, we identify the X-linked mental retardation protein OPHN1 as a molecule essential for mGluR-LTD in the hippocampus. mGluR-LTD induction elicits rapid dendritic OPHN1 synthesis, which is dependent on mGluR1 activation and independent of fragile X mental retardation protein (FMRP). This response is essential for mGluR-LTD, as acute blockade of OPHN1 synthesis impedes LTD. mGluR-induced OPHN1 mediates LTD and associated persistent decreases in surface AMPARs via interactions with endophilin A2/3. Importantly, this role of OPHN1 is separable from its effects on basal synaptic strength, which require OPHN1's Rho-GAP activity and interaction with Homer1b/c. Thus, our data establish a role for rapid OPHN1 synthesis in mGluR-LTD. VIDEO ABSTRACT:

Item Type: Paper
Subjects: diseases & disorders > congenital hereditary genetic diseases
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor
diseases & disorders > congenital hereditary genetic diseases > mental retardation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: Matt Covey
Date: 20 October 2011
Date Deposited: 05 Feb 2013 21:15
Last Modified: 26 Dec 2014 19:59
PMCID: PMC3206629
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27182

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