The delta2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity.
The delta2 glutamate receptor (GluRdelta2) belongs to the ionotropic glutamate receptor (iGluR) family and plays a crucial role in the induction of cerebellar long-term depression (LTD), a form of synaptic plasticity underlying motor learning. Nevertheless, the mechanisms by which GluRdelta2 regulates cerebellar LTD have remained elusive. Because a mutation occurring in lurcher mice causes continuous GluRdelta2 channel activity that can be abolished by 1-naphtylacetylspermine (NASP), a channel blocker for Ca(2+)-permeable iGluRs, GluRdelta2 is thought to function as an ion channel. Here, we introduced a mutant GluRdelta2 transgene, in which the putative channel pore was disrupted, into GluRdelta2-null Purkinje cells using a virus vector. Surprisingly and similar to the effect of the wild-type GluRdelta2 transgene, the mutant GluRdelta2 completely rescued the abrogated LTD in GluRdelta2-null mice. Furthermore, NASP did not block LTD induction in wild-type cerebellar slices. These results indicate that GluRdelta2, a member of the iGluR family, does not serve as a channel in the regulation of LTD induction.
Kakegawa
Wataru
W
Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Kohda
Kazuhisa
K
Yuzaki
Michisuke
M
D000818:Animals; D002460:Cell Line; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D011689:Purkinje Cells / Q000502:physiology*; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*; D013096:Spermine / Q000031:analogs & derivatives
D007473:Ion Channels; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2; C067506:1-naphthylacetylspermine; D013096:Spermine
J Physiol. 2007 Mar 15;579(Pt 3):729-35
17255161
J Physiol. 1999 Oct 15;520 Pt 2:337-57
10523404
Nat Neurosci. 2000 Apr;3(4):315-22
10725919
J Biol Chem. 2000 May 26;275(21):16167-73
10748123
J Neurosci. 2000 Aug 15;20(16):5973-80
10934245
Science. 2001 May 4;292(5518):926-9
11340205
J Neurosci. 2002 Feb 1;22(3):803-14
11826110
Neuron. 2002 Mar 28;34(1):107-14
11931745
Neuroscience. 2002;115(4):1199-210
12453491
Trends Neurosci. 2003 Jan;26(1):27-32
12495860
Biochem Biophys Res Commun. 2003 Feb 21;301(4):1122-8
12589829
Nat Neurosci. 2003 Aug;6(8):869-76
12833050
Nature. 2003 Aug 7;424(6949):677-81
12904794
J Neurosci. 2003 Nov 5;23(31):10064-73
14602821
Cerebellum. 2004;3(2):89-93
15233575
Annu Rev Neurosci. 1989;12:85-102
2648961
Neuron. 1992 Jan;8(1):189-98
1370372
Science. 1992 Jun 12;256(5063):1563-6
1317969
J Neurosci. 1992 Oct;12(10):4080-7
1357118
FEBS Lett. 1993 Jan 11;315(3):318-22
8422924
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1267-76
7506541
Annu Rev Neurosci. 1994;17:31-108
8210177
Cell. 1995 Apr 21;81(2):245-52
7736576
Neuron. 1995 Aug;15(2):453-62
7646897
Nature. 1997 Aug 21;388(6644):769-73
9285588
Neurosci Res. 1997 Sep;29(1):27-36
9293490
J Neurosci. 1997 Jan 15;17(2):834-42
8987804
Nature. 1999 Jan 7;397(6714):72-6
9892356
J Neurosci. 1999 May 15;19(10):3926-34
10234023
Eur J Neurosci. 2007 Mar;25(5):1357-62
17425562