N-methyl-D-aspartate Receptors Mediate the Phosphorylation and Desensitization of Muscarinic Receptors in Cerebellar Granule Neurons

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Apr 1

PMID 19332541

Citations 7

Authors

Adrian J Butcher

Ignacio Torrecilla

Kenneth W Young

Kok Choi Kong

Sharad C Mistry

Andrew R Bottrill

Andrew B Tobin

Affiliations

Soon will be listed here.

Abstract

Changes in synaptic strength mediated by ionotropic glutamate N-methyl-D-asparate (NMDA) receptors is generally considered to be the molecular mechanism underlying memory and learning. NMDA receptors themselves are subject to regulation through signaling pathways that are activated by G-protein-coupled receptors (GPCRs). In this study we investigate the ability of NMDA receptors to regulate the signaling of GPCRs by focusing on the G(q/11)-coupled M(3)-muscarinic receptor expressed endogenously in mouse cerebellar granule neurons. We show that NMDA receptor activation results in the phosphorylation and desensitization of M(3)-muscarinic receptors through a mechanism dependent on NMDA-mediated calcium influx and the activity of calcium-calmodulin-dependent protein kinase II. Our study reveals a complex pattern of regulation where GPCRs (M(3)-muscarinic) and NMDA receptors can feedback on each other in a process that is likely to influence the threshold value of signaling networks involved in synaptic plasticity.

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References

Macdonald J, Jackson M, Beazely M . G protein-coupled receptors control NMDARs and metaplasticity in the hippocampus. Biochim Biophys Acta. 2007; 1768(4):941-51. DOI: 10.1016/j.bbamem.2006.12.006. View

Watabe A, Zaki P, ODell T . Coactivation of beta-adrenergic and cholinergic receptors enhances the induction of long-term potentiation and synergistically activates mitogen-activated protein kinase in the hippocampal CA1 region. J Neurosci. 2000; 20(16):5924-31. PMC: 6772603. View

Watkins J, Jane D . The glutamate story. Br J Pharmacol. 2006; 147 Suppl 1:S100-8. PMC: 1760733. DOI: 10.1038/sj.bjp.0706444. View

Torrecilla I, Spragg E, Poulin B, McWilliams P, Mistry S, Blaukat A . Phosphorylation and regulation of a G protein-coupled receptor by protein kinase CK2. J Cell Biol. 2007; 177(1):127-37. PMC: 2064117. DOI: 10.1083/jcb.200610018. View

Shinoe T, Matsui M, Taketo M, Manabe T . Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus. J Neurosci. 2005; 25(48):11194-200. PMC: 6725656. DOI: 10.1523/JNEUROSCI.2338-05.2005. View

McCutchen E, Scheiderer C, Dobrunz L, McMahon L . Coexistence of muscarinic long-term depression with electrically induced long-term potentiation and depression at CA3-CA1 synapses. J Neurophysiol. 2006; 96(6):3114-21. DOI: 10.1152/jn.00144.2006. View

Abraham W, Bear M . Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 1996; 19(4):126-30. DOI: 10.1016/s0166-2236(96)80018-x. View

Leist M, Volbracht C, Kuhnle S, Fava E, Ferrando-May E, Nicotera P . Caspase-mediated apoptosis in neuronal excitotoxicity triggered by nitric oxide. Mol Med. 1998; 3(11):750-64. PMC: 2230245. View

Auerbach J, Segal M . Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus. J Physiol. 1996; 492 ( Pt 2):479-93. PMC: 1158842. DOI: 10.1113/jphysiol.1996.sp021323. View

10.

Budd D, McDonald J, Tobin A . Phosphorylation and regulation of a Gq/11-coupled receptor by casein kinase 1alpha. J Biol Chem. 2000; 275(26):19667-75. DOI: 10.1074/jbc.M000492200. View

11.

Hirose K, Kadowaki S, Tanabe M, Takeshima H, Iino M . Spatiotemporal dynamics of inositol 1,4,5-trisphosphate that underlies complex Ca2+ mobilization patterns. Science. 1999; 284(5419):1527-30. DOI: 10.1126/science.284.5419.1527. View

12.

Young K, Nash M, Challiss R, Nahorski S . Role of Ca2+ feedback on single cell inositol 1,4,5-trisphosphate oscillations mediated by G-protein-coupled receptors. J Biol Chem. 2003; 278(23):20753-60. DOI: 10.1074/jbc.M211555200. View

13.

Okubo Y, Kakizawa S, Hirose K, Iino M . Visualization of IP(3) dynamics reveals a novel AMPA receptor-triggered IP(3) production pathway mediated by voltage-dependent Ca(2+) influx in Purkinje cells. Neuron. 2001; 32(1):113-22. DOI: 10.1016/s0896-6273(01)00464-0. View

14.

Perkins D, Pappin D, Creasy D, Cottrell J . Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis. 1999; 20(18):3551-67. DOI: 10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2. View

15.

Lisman J, Schulman H, Cline H . The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci. 2002; 3(3):175-90. DOI: 10.1038/nrn753. View

16.

Tobin A, Butcher A, Kong K . Location, location, location...site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling. Trends Pharmacol Sci. 2008; 29(8):413-20. PMC: 2880250. DOI: 10.1016/j.tips.2008.05.006. View

17.

Bortolotto Z, Bashir Z, Davies C, Collingridge G . A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation. Nature. 1994; 368(6473):740-3. DOI: 10.1038/368740a0. View

18.

DeBock F, Kurz J, Azad S, Parsons C, Hapfelmeier G, Zieglgansberger W . Alpha2-adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o-protein-mediated modulation of Ca2+-channels and inwardly rectifying K+-channels in LTD. Eur J Neurosci. 2003; 17(7):1411-24. DOI: 10.1046/j.1460-9568.2003.02544.x. View

19.

Budd D, Willars G, McDonald J, Tobin A . Phosphorylation of the Gq/11-coupled m3-muscarinic receptor is involved in receptor activation of the ERK-1/2 mitogen-activated protein kinase pathway. J Biol Chem. 2000; 276(7):4581-7. DOI: 10.1074/jbc.M008827200. View

20.

Bliss T, Collingridge G . A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993; 361(6407):31-9. DOI: 10.1038/361031a0. View