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EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP

Nature Neuroscience volume 5, pages 1117–1118 (2002)Cite this article

Abstract

Dendritic spines show structural plasticity during development and in response to synaptic activity1,2,3. We previously found that EphB2 receptor tyrosine kinase, a receptor for B-ephrin ligands, is functionally involved in spine morphogenesis4, but the downstream signaling mechanisms are not known. Here we show that EphB2 physically associates with the guanine nucleotide exchange factor (GEF) intersectin and activates its GEF activity in cooperation with neural Wiskott-Aldrich syndrome protein (N-WASP), which in turn activates the Rho-family GTPase Cdc42 and spine morphogenesis.

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Figure 1: Cdc42 is activated by EphB–intersectin signaling.
Figure 2: Association of EphB2 with intersectin-l.
Figure 3: Effects of dominant-negative constructs on spine formation.

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Acknowledgements

We thank E. B. Pasquale for helpful discussion, and Pasquale, P. S. McPherson and G. M. Bokoch for their gifts of antibodies and expression vectors. This work was supported by HD25938 from the National Institutes of Health.

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  1. The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, California, USA

    Fumitoshi Irie & Yu Yamaguchi

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  1. Fumitoshi Irie
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  2. Yu Yamaguchi
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Correspondence to Yu Yamaguchi.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1.

Domains involved in the EphB2/intersectin interaction. (a) Interaction of EphB2 deletion mutants with the full-length intersectin-l. Deletion constructs used in the experiment were shown in the left panel. The full-length and ΔCT EphB2 were coimmunoprecipitated with intersectin-l, whereas deletion mutants lacking the TK domain were not. TM: transmembrane, JM: juxtamembrane, TK: tyrosine kinase, CT: C-terminal tail. (b) Interaction of intersectin deletion mutants with the full-length EphB2. Deletion constructs used in the experiment were shown in the left panel. EphB2 was coimmunoprecipitated with both intersectin-l and intersectin-s, but not with a fragment consisting only of the DH, PH, and C2 domains (DPC). EH: Eps15 homology, CC: coiled coil, SH3: Src homology 3, DH: Dbl homology, PH: pleckstrin homology, C2: protein kinase C conserved region 2. IP: immunoprecipitation; IB: immunoblotting. (JPG 26 kb)

Supplementary Fig. 2.

Coimmunoprecipitation of intersectin and syndecan-2 from adult mouse synaptosomes. Lysates from adult mouse synaptosomes were incubated for 4 h at 4°C with Protein G-agarose charged with monoclonal anti-syndecan-2 antibody (6G12) or control mouse IgG. The immunoprecipitated materials were probed with anti-intersectin (upper panel) or anti-syndecan-2 (lower panel) antibodies. (JPG 14 kb)

Supplementary Fig. 3.

Colocalization of intersectin, N-WASP, and EphB2 in dendritic spines. (a) Dissociated mouse hippocampal neurons at 21 DIV were double-stained for intersectin and EphB2 (upper panels) or for N-WASP and EphB2 (lower panels). (b) Hippocampal neurons transfected with pEGFP-N1 at 10 d.i.v. (to visualize spines) were immunostained for intersectin (left panels) or N-WASP (right panels) at 21 d.i.v. Scale bars, (a) 5 μm; (b) 1 μm. (JPG 39 kb)

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Irie, F., Yamaguchi, Y. EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP. Nat Neurosci 5, 1117–1118 (2002). https://doi.org/10.1038/nn964

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