Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation.
Trafficking of AMPA receptors (AMPARs) is important for many forms of synaptic plasticity. However, the link between activity and resulting synaptic alterations is not fully understood. We identified a direct interaction between N-ethylmaleimide-sensitive fusion protein (NSF), an ATPase involved in membrane fusion events and stabilization of surface AMPARs, and Polo-like kinase- 2 (Plk2), an activity-inducible kinase that homeostatically decreases excitatory synapse number and strength. Plk2 disrupted the interaction of NSF with the GluA2 subunit of AMPARs, promoting extensive loss of surface GluA2 in rat hippocampal neurons, greater association of GluA2 with adaptor proteins PICK1 and GRIP1, and decreased synaptic AMPAR current. Plk2 engagement of NSF, but not Plk2 kinase activity, was required for this mechanism and occurred through a motif in the Plk2 protein that was independent of the canonical polo box interaction sites. These data reveal that heightened synaptic activity, acting through Plk2, leads to homeostatic decreases in surface AMPAR expression via the direct dissociation of NSF from GluA2.
Evers
Danielle M
DM
Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.
Matta
Jose A
JA
Hoe
Hyang-Sook
HS
Zarkowsky
Devin
D
Lee
Sang Hyoung
SH
Isaac
John T
JT
Pak
Daniel T S
DT
D000255:Adenosine Triphosphate / Q000494:pharmacology; D020816:Amino Acid Motifs / Q000235:genetics / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D018613:Microscopy, Confocal / Q000379:methods; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods
D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018756:GABA Antagonists; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010852:Picrotoxin; D017346:Protein Serine-Threonine Kinases; D018091:Receptors, AMPA; C491308:Grip1 protein, rat; C498298:PICK1 protein, rat; C530504:Plk2 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2
J Biol Chem. 2008 Oct 24;283(43):29424-32
18723513
J Neurosci. 2007 Dec 12;27(50):13903-8
18077702
Neuron. 2002 Mar 28;34(1):53-67
11931741
Neuron. 1999 Oct;24(2):389-99
10571232
Neuron. 1998 Aug;21(2):393-400
9728920
J Neurosci. 2001 Aug 1;21(15):5417-28
11466413
Mol Cell Neurosci. 2008 Jun;38(2):189-202
18417360
J Neurosci. 2000 Oct 1;20(19):7258-67
11007883
J Neurosci. 2008 Jul 30;28(31):7820-7
18667614
Mol Cell Neurosci. 2005 Apr;28(4):650-60
15797712
Neuron. 2005 Mar 24;45(6):903-15
15797551
J Neurosci. 2006 May 17;26(20):5309-19
16707783
Nat Neurosci. 2006 May;9(5):602-4
16582904
Neuron. 1999 Jun;23(2):365-76
10399941
J Cell Biol. 2005 May 9;169(3):399-404
15883194
Curr Opin Neurobiol. 2007 Jun;17(3):318-24
17451937
Mol Cell Biol. 1992 Sep;12(9):4164-9
1508211
Proc Natl Acad Sci U S A. 2002 May 14;99(10):7096-101
12011465
Neuron. 2003 Jul 3;39(1):163-76
12848940
Cell. 2001 Jun 29;105(7):825-8
11439178
Cell. 2001 May 4;105(3):331-43
11348590
Neuron. 2000 Nov;28(2):499-510
11144359
Neuron. 1996 Nov;17(5):945-56
8938126
Ann N Y Acad Sci. 1999 Apr 30;868:535-40
10414331
Neuron. 1999 Nov;24(3):649-58
10595516
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1038-43
18195348
Neuron. 2005 May 19;46(4):533-40
15944123
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9301-6
9689075
J Biol Chem. 2002 Oct 25;277(43):40901-10
12130635
Neuron. 2000 Dec;28(3):873-86
11163273
Neuropharmacology. 2007 Jan;52(1):156-75
16949624
Cell. 2003 Oct 3;115(1):83-95
14532005
Neuron. 1998 Jul;21(1):99-110
9697855
Neuron. 2000 Aug;27(2):313-25
10985351
Biochem J. 1999 Apr 15;339 ( Pt 2):435-42
10191277
Neuron. 2002 Nov 14;36(4):661-74
12441055
Neuron. 2009 Apr 30;62(2):254-68
19409270
Neuron. 1998 Jul;21(1):87-97
9697854
Science. 2003 Nov 21;302(5649):1368-73
14576440
FEBS Lett. 2007 May 22;581(11):2140-9
17397838
Neuron. 2006 Nov 9;52(3):475-84
17088213
J Neurosci. 1996 Mar 15;16(6):1982-9
8604042
J Neurosci. 2008 Jun 25;28(26):6583-91
18579731
J Neurosci. 2002 May 1;22(9):3493-503
11978826
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11725-30
11573007
Neuron. 2008 May 22;58(4):571-83
18498738
J Neurosci. 2009 May 20;29(20):6479-89
19458219
J Neurosci. 2004 Jun 9;24(23):5381-90
15190111
Neuron. 2001 Aug 2;31(2):289-303
11502259
EMBO J. 1999 Oct 15;18(20):5528-39
10523297