TY - JOUR
T1 - A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-
AU - Dickinson, Bryony A.
AU - Jo, Jihoon
AU - Seok, Heon
AU - Son, Gi Hoon
AU - Whitcomb, Daniel J.
AU - Davies, Ceri H.
AU - Sheng, Morgan
AU - Collingridge, Graham L.
AU - Cho, Kwangwook
N1 - 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.
PY - 2009
Y1 - 2009
N2 - 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-.
AB - 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-.
UR - http://www.scopus.com/inward/record.url?scp=68149170171&partnerID=8YFLogxK
U2 - 10.1186/1756-6606-2-18
DO - 10.1186/1756-6606-2-18
M3 - Article
C2 - 19534762
AN - SCOPUS:68149170171
SN - 1756-6606
VL - 2
JO - Molecular brain
JF - Molecular brain
IS - 1
M1 - 18
ER -