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Neuron. 2011 Oct 20;72(2):300-15. doi: 10.1016/j.neuron.2011.09.001.

Rapid synthesis of the X-linked mental retardation protein OPHN1 mediates mGluR-dependent LTD through interaction with the endocytic machinery.

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1
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.

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.

PMID:
22017989
PMCID:
PMC3206629
DOI:
10.1016/j.neuron.2011.09.001
[Indexed for MEDLINE]
Free PMC Article
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