Hook-up of GluA2, GRIP and liprin-alpha for cholinergic muscarinic receptor-dependent LTD in the hippocampus.
The molecular mechanism underlying muscarinic acetylcholine receptor-dependent LTD (mAChR-LTD) in the hippocampus is less studied. In a recent study, a novel mechanism is described. The induction of mAChR-LTD required the activation of protein tyrosine phosphatase (PTP), and the expression was mediated by AMPA receptor endocytosis via interactions between GluA2, GRIP and liprin-alpha. The hook-up of these proteins may result in the recruitment of leukocyte common antigen-related receptor (LAR), a PTP that is known to be involved in AMPA receptor trafficking. Interestingly, the similar molecular interaction cannot be applied to mGluR-LTD, despite the fact that the same G-protein involved in LTD is activated by both mAChR and mGluR. This discovery provides key molecular insights for cholinergic dependent cognitive function, and mAChR-LTD can serve as a useful cellular model for studying the roles of cholinergic mechanism in learning and memory.
Wu
Long-Jun
LJ
Wang
Yu-Tian
YT
Zhuo
Min
M
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D002352:Carrier Proteins; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D011976:Receptors, Muscarinic; D002217:Carbachol; C104722:glutamate receptor ionotropic, AMPA 2