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 acethycholine 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-. 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-. 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-. 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-.
Original language | English |
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Article number | 18 |
Journal | Molecular brain |
Volume | 2 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2009 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by the BBSRC (KC), UK Alzheimer Research Trust (KC, GLC) and the MRC (KC, GLC). GLC is a Wolfson-Royal Society fellow.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience