Home LiteratureArticle Details
PMID: 21147983 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 30 ·No. 49 ·2010-12-08 ·Pages 16437-52

Citri A, Bhattacharyya S, Ma C, Morishita W, Fang S, Rizo J, Malenka RC

Abstract

NMDA receptor (NMDAR)-dependent long-term depression (LTD) in the hippocampus is mediated primarily by the calcium-dependent removal of AMPA receptors (AMPARs) from the postsynaptic density. The AMPAR-binding, PDZ (PSD-95/Dlg/ZO1) and BAR (Bin/amphiphysin/Rvs) domain-containing protein PICK1 has been implicated in the regulation of AMPAR trafficking underlying several forms of synaptic plasticity. Using a strategy involving small hairpin RNA-mediated knockdown of PICK1 and its replacement with recombinant PICK1, we performed a detailed structure-function analysis of the role of PICK1 in hippocampal synaptic plasticity and the underlying NMDAR-induced AMPAR trafficking. We found that PICK1 is not necessary for maintenance of the basal synaptic complement of AMPARs or expression of either metabotropic glutamate receptor-dependent LTD or NMDAR-dependent LTP. Rather, PICK1 function is specific to NMDAR-dependent LTD and the underlying AMPAR trafficking. Furthermore, although PICK1 does not regulate the initial phase of NMDAR-induced AMPAR endocytosis, it is required for intracellular retention of internalized AMPARs. Detailed biophysical analysis of an N-terminal acidic motif indicated that it is involved in intramolecular electrostatic interactions that are disrupted by calcium. Mutations that interfered with the calcium-induced structural changes in PICK1 precluded LTD and the underlying NMDAR-induced intracellular retention of AMPARs. These findings support a model whereby calcium-induced modification of PICK1 structure is critical for its function in the retention of internalized AMPARs that underlies the expression of hippocampal NMDAR-dependent LTD.

MeSH Terms
Animals Animals, Newborn Calcium/metabolism,pharmacology Carrier Proteins/genetics,metabolism Cell Membrane/drug effects,metabolism Cells, Cultured Cytoskeletal Proteins Drug Interactions Electric Stimulation/methods Excitatory Amino Acid Agents/pharmacology Excitatory Postsynaptic Potentials/drug effects,genetics Green Fluorescent Proteins/genetics Hippocampus/cytology Humans Immunoprecipitation/methods Long-Term Synaptic Depression/drug effects,physiology Methoxyhydroxyphenylglycol/analogs & derivatives,pharmacology Mutation/genetics Neurons/drug effects,physiology Nuclear Proteins/genetics,metabolism Patch-Clamp Techniques/methods Protein Binding/drug effects Protein Structure, Tertiary/genetics,physiology Protein Transport/drug effects,physiology RNA, Small Interfering/pharmacology Rats Rats, Sprague-Dawley Receptors, AMPA/metabolism
Chemicals
Carrier Proteins Cytoskeletal Proteins Excitatory Amino Acid Agents Nuclear Proteins PICK1 protein, rat RNA, Small Interfering Receptors, AMPA Green Fluorescent Proteins Methoxyhydroxyphenylglycol Calcium 3,4-dihydroxyphenylglycol
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Citri Ami
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 94304, USA.
Bhattacharyya Samarjit
Ma Cong
Morishita Wade
Fang Scarlett
Rizo Josep
Malenka Robert C
References (51)
51 references, click to expand
  1. The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits.
    Neuropharmacology. 1999 May;38(5):635-44 PMID: 10340301
  2. Role of AMPA receptor endocytosis in synaptic plasticity.
    Nat Rev Neurosci. 2001 May;2(5):315-24 PMID: 11331915
  3. Endocytosis and recycling of AMPA receptors lacking GluR2/3.
    Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1038-43 PMID: 18195348
  4. PICK1 and phosphorylation of the glutamate receptor 2 (GluR2) AMPA receptor subunit regulates GluR2 recycling after NMDA receptor-induced internalization.
    J Neurosci. 2007 Dec 12;27(50):13903-8 PMID: 18077702
  5. AMPA receptor trafficking at excitatory synapses.
    Neuron. 2003 Oct 9;40(2):361-79 PMID: 14556714
  6. Organelles and trafficking machinery for postsynaptic plasticity.
    Annu Rev Neurosci. 2006;29:325-62 PMID: 16776589
  7. An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity.
    Neuron. 2008 Mar 27;57(6):872-82 PMID: 18367088
  8. Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins.
    J Neurosci. 2000 Oct 1;20(19):7258-67 PMID: 11007883
  9. Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses.
    Nat Neurosci. 2005 Jun;8(6):768-75 PMID: 15895086
  10. Protein kinase Cdelta and calmodulin regulate epidermal growth factor receptor recycling from early endosomes through Arp2/3 complex and cortactin.
    Mol Biol Cell. 2008 Jan;19(1):17-29 PMID: 17959830
  11. A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors.
    Nat Neurosci. 2009 Feb;12(2):172-81 PMID: 19169250
  12. Synapse-specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins.
    Neuron. 2006 Oct 19;52(2):307-20 PMID: 17046693
  13. PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking.
    EMBO J. 2005 Sep 21;24(18):3266-78 PMID: 16138078
  14. Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD.
    Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):413-8 PMID: 20018661
  15. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex.
    Dev Cell. 2009 Nov;17(5):712-23 PMID: 19922875
  16. LTP and LTD: an embarrassment of riches.
    Neuron. 2004 Sep 30;44(1):5-21 PMID: 15450156
  17. The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands.
    J Biol Chem. 2004 Oct 1;279(40):41393-7 PMID: 15247289
  18. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins.
    Neuron. 2000 Nov;28(2):499-510 PMID: 11144359
  19. PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses.
    Neuron. 2000 Dec;28(3):873-86 PMID: 11163273
  20. Molecular dissociation of the role of PSD-95 in regulating synaptic strength and LTD.
    Neuron. 2008 Jan 24;57(2):248-62 PMID: 18215622
  21. Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression.
    Neuron. 2006 Mar 16;49(6):845-60 PMID: 16543133
  22. Dynamin-dependent endocytosis of ionotropic glutamate receptors.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14112-7 PMID: 10570207
  23. Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization.
    Nat Neurosci. 2000 Dec;3(12):1282-90 PMID: 11100149
  24. Synaptic plasticity: multiple forms, functions, and mechanisms.
    Neuropsychopharmacology. 2008 Jan;33(1):18-41 PMID: 17728696
  25. Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression.
    Science. 2003 Jun 13;300(5626):1751-5 PMID: 12805550
  26. NSF ATPase and alpha-/beta-SNAPs disassemble the AMPA receptor-PICK1 complex.
    Neuron. 2002 Mar 28;34(1):53-67 PMID: 11931741
  27. Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels.
    Mol Biol Cell. 2007 Aug;18(8):3105-18 PMID: 17553932
  28. NMDA receptors mediate calcium-dependent, bidirectional changes in dendritic PICK1 clustering.
    Mol Cell Neurosci. 2006 Mar;31(3):574-85 PMID: 16406232
  29. Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1.
    Neuron. 2008 Dec 26;60(6):1095-111 PMID: 19109914
  30. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1.
    Neuron. 1999 Jan;22(1):179-87 PMID: 10027300
  31. The cell biology of synaptic plasticity: AMPA receptor trafficking.
    Annu Rev Cell Dev Biol. 2007;23:613-43 PMID: 17506699
  32. Alternative N-terminal domains of PSD-95 and SAP97 govern activity-dependent regulation of synaptic AMPA receptor function.
    Neuron. 2006 Jul 6;51(1):99-111 PMID: 16815335
  33. Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity.
    J Neurosci. 2006 Mar 1;26(9):2380-90 PMID: 16510715
  34. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure.
    Science. 2004 Jan 23;303(5657):495-9 PMID: 14645856
  35. AMPA receptor trafficking and synaptic plasticity.
    Annu Rev Neurosci. 2002;25:103-26 PMID: 12052905
  36. Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha.
    J Biol Chem. 1997 Dec 19;272(51):32019-24 PMID: 9405395
  37. Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11725-30 PMID: 11573007
  38. PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2.
    J Neurosci. 2001 Aug 1;21(15):5417-28 PMID: 11466413
  39. Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD.
    Nat Neurosci. 2000 Dec;3(12):1291-300 PMID: 11100150
  40. Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis.
    Nat Cell Biol. 2008 Mar;10(3):259-71 PMID: 18297063
  41. Regulation of synaptic strength and AMPA receptor subunit composition by PICK1.
    J Neurosci. 2004 Jun 9;24(23):5381-90 PMID: 15190111
  42. PICK1: a multi-talented modulator of AMPA receptor trafficking.
    Pharmacol Ther. 2008 Apr;118(1):152-60 PMID: 18353440
  43. GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity.
    Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):715-20 PMID: 12740117
  44. Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells.
    Neuron. 1997 Jun;18(6):969-82 PMID: 9208864
  45. Effects of PKA and PKC on miniature excitatory postsynaptic currents in CA1 pyramidal cells.
    J Neurophysiol. 1998 Nov;80(5):2797-800 PMID: 9819284
  46. Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF.
    Neuron. 2005 Mar 24;45(6):903-15 PMID: 15797551
  47. Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting.
    Neuron. 2000 Nov;28(2):511-25 PMID: 11144360
  48. N-methyl-D-aspartate receptor- and metabotropic glutamate receptor-dependent long-term depression are differentially regulated by the ubiquitin-proteasome system.
    Eur J Neurosci. 2009 Oct;30(8):1443-50 PMID: 19821836
  49. Transsynaptic signaling by postsynaptic synapse-associated protein 97.
    J Neurosci. 2006 Feb 22;26(8):2343-57 PMID: 16495462
  50. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease.
    Neuron. 2010 Feb 25;65(4):445-59 PMID: 20188650
  51. PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking.
    Neuron. 2005 Aug 4;47(3):407-21 PMID: 16055064
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4478-10.2010
Published
2010-12-08
Pages
16437-52
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC3004477
Subset
IM
Grants
NIMH NIH HHS · R01 MH063394 · United States
NINDS NIH HHS · R01 NS037200 · United States
NIMH NIH HHS · R37 MH063394-19 · United States
NIMH NIH HHS · P50 MH086403 · United States
NIMH NIH HHS · R37 MH063394-20 · United States
NIMH NIH HHS · R37 MH063394 · United States
NIMH NIH HHS · R37 MH063394-21 · United States
NINDS NIH HHS · NS37200 · United States
NIMH NIH HHS · MH63394 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4478-10.2010 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2