The N-Terminal Domain of GluD2 (GluRδ2) Recruits Presynaptic Terminals and Regulates Synaptogenesis in the Cerebellum In Vivo

被引:51
作者
Kakegawa, Wataru
Miyazaki, Taisuke [2 ]
Kohda, Kazuhisa
Matsuda, Keiko
Emi, Kyoichi
Motohashi, Junko
Watanabe, Masahiko [2 ]
Yuzaki, Michisuke [1 ]
机构
[1] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 1608582, Japan
[2] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan
关键词
DELTA-2; GLUTAMATE-RECEPTOR; CLIMBING FIBER TERRITORY; PURKINJE-CELLS; SYNAPTIC PLASTICITY; MOTOR COORDINATION; KAINATE RECEPTORS; MUTANT MICE; MULTIPLE INNERVATION; EXCITATORY SYNAPSES; ADHESION MOLECULE;
D O I
10.1523/JNEUROSCI.6013-08.2009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The delta 2 glutamate receptor (GluR delta 2; GluD2), which is predominantly expressed on postsynaptic sites at parallel fiber (PF)-Purkinje cell synapses in the cerebellum, plays two crucial roles in the cerebellum: the formation of PF synapses and the regulation of long-term depression (LTD), a form of synaptic plasticity underlying motor learning. Although the induction of LTD and motor learning absolutely require signaling via the cytoplasmic C-terminal domain of GluD2, the mechanisms by which GluD2 regulates PF synaptogenesis have remained unclear. Here, we examined the role of the extracellular N-terminal domain (NTD) of GluD2 on PF synaptogenesis by injecting Sindbis virus carrying wild-type (GluD2(wt)) or mutant GluD2 into the subarachnoid supracerebellar space of GluD2-null mice. Remarkably, the expression of GluD2(wt), but not of a mutant GluD2 lacking the NTD (GluD2(Delta NTD)), rapidly induced PF synapse formation and rescued gross motor dyscoordination in adult GluD2-null mice just 1 d after injection. In addition, although the kainate receptor GluR6 (GluK2) did not induce PF synaptogenesis, a chimeric GluK2 that contained the NTD of GluD2 (GluD2(NTD)-GluK2) did. Similarly, GluD2(wt) and GluD2(NTD)-GluK2, but not GluD2(Delta NTD), induced synaptogenesis in heterologous cells in vitro. In contrast, LTD was restored in GluD2-null Purkinje cells expressing a mutant GluD2 lacking the NTD. These results indicate that the NTD of GluD2 is necessary and sufficient for the function of GluD2 in the regulation of PF -Purkinje cell synaptogenesis. Furthermore, our results suggest that GluD2 differently regulates PF synaptogenesis and cerebellar LTD through the extracellular NTD and the cytoplasmic C-terminal end, respectively.
引用
收藏
页码:5738 / 5748
页数:11
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