QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 6, 2009, 29(18):5738-5748; doi:10.1523/JNEUROSCI.6013-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Kakegawa, W. Articles by Yuzaki, M. Search for Related Content PubMed PubMed Citation Articles by Kakegawa, W. Articles by Yuzaki, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The N-Terminal Domain of GluD2 (GluR2) Recruits Presynaptic Terminals and Regulates Synaptogenesis in the Cerebellum In Vivo

Wataru Kakegawa,^1 * Taisuke Miyazaki,^2 * Kazuhisa Kohda,¹ Keiko Matsuda,¹ Kyoichi Emi,¹ Junko Motohashi,¹ Masahiko Watanabe,² and Michisuke Yuzaki¹

¹Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan, and ²Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638 Japan

Correspondence should be addressed to Michisuke Yuzaki, Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: myuzaki{at}a5.keio.jp

The 2 glutamate receptor (GluR2; 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^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^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.

---

Received Dec. 18, 2008; revised March 15, 2009; accepted March 25, 2009.

Correspondence should be addressed to Michisuke Yuzaki, Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: myuzaki{at}a5.keio.jp

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2009 29: i. [Full Text]  

This article has been cited by other articles:

				J.-M. Sobotzik, J. M. Sie, C. Politi, D. Del Turco, V. Bennett, T. Deller, and C. Schultz AnkyrinG is required to maintain axo-dendritic polarity in vivo PNAS, October 13, 2009; 106(41): 17564 - 17569. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help