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Mol Brain. 2009 Jun 17;2:18. doi: 10.1186/1756-6606-2-18.

A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-alpha.

Author information

  • 1Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Medicine and Dentistry, University of Bristol, Whitson Street, Bristol BS1 3NY, UK. b.dickinson@bristol.ac.uk

Abstract

BACKGROUND:

Long-term depression (LTD) in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors (mAChRs). Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC), it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-alpha.

RESULTS:

Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-alpha. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms.

CONCLUSION:

Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-alpha. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-alpha.

PMID:
19534762
[PubMed - indexed for MEDLINE]
PMCID:
PMC2701934
Free PMC Article
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