Structural basis for integration of GluD receptors within synaptic organizer complexes

Jonathan Elegheert, Wataru Kakegawa, Jordan E. Clay, Natalie F. Shanks, Ester Behiels, Keiko Matsuda, Kazuhisa Kohda, Eriko Miura, Maxim Rossmann, Nikolaos Mitakidis, Junko Motohashi, Veronica T. Chang, Christian Siebold, Ingo H. Greger, Terunaga Nakagawa, Michisuke Yuzaki, A. Radu Aricescu

研究成果: Article

52 引用 (Scopus)

抜粋

Ionotropic glutamate receptor (iGluR) family members are integrated into supramolecular complexes that modulate their location and function at excitatory synapses. However, a lack of structural information beyond isolated receptors or fragments thereof currently limits the mechanistic understanding of physiological iGluR signaling. Here, we report structural and functional analyses of the prototypical molecular bridge linking postsynaptic iGluR δ2 (GluD2) and presynaptic β-neurexin 1 (β-NRX1) via Cbln1, a C1q-like synaptic organizer. We show how Cbln1 hexamers "anchor" GluD2 amino-terminal domain dimers to monomeric β-NRX1. This arrangement promotes synaptogenesis and is essential for D-serine-dependent GluD2 signaling in vivo, which underlies long-term depression of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses and motor coordination in developing mice. These results lead to a model where protein and small-molecule ligands synergistically control synaptic iGluR function.

元の言語English
ページ(範囲)295-300
ページ数6
ジャーナルScience
353
発行部数6296
DOI
出版物ステータスPublished - 2016 7 15

ASJC Scopus subject areas

  • General

フィンガープリント Structural basis for integration of GluD receptors within synaptic organizer complexes' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Elegheert, J., Kakegawa, W., Clay, J. E., Shanks, N. F., Behiels, E., Matsuda, K., Kohda, K., Miura, E., Rossmann, M., Mitakidis, N., Motohashi, J., Chang, V. T., Siebold, C., Greger, I. H., Nakagawa, T., Yuzaki, M., & Aricescu, A. R. (2016). Structural basis for integration of GluD receptors within synaptic organizer complexes. Science, 353(6296), 295-300. https://doi.org/10.1126/science.aae0104