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Published online 29 November 2004. doi:10.1083/jcb.200406030
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 5, 961-972
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Article

Cadherin activity is required for activity-induced spine remodeling



Ko Okamura1, Hidekazu Tanaka1, Yoshiki Yagita2,3, Yoshinaga Saeki4, Akihiko Taguchi5, Yasushi Hiraoka6, Ling-Hui Zeng1, David R Colman3, and Naomasa Miki1

1 Department of Pharmacology, Osaka University Medical School, Suita, Osaka 565-0871 Japan
2 Department of Internal Medicine, Osaka University Medical School, Suita, Osaka 565-0871 Japan
3 The Montreal Neurological Institute, Montreal, Quebec H3A 2B4
4 Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown, MA 02114
5 National Cardiovascular Center, Suita, Osaka 565-8565 Japan
6 Kansai Advanced Research Center, National Institute of Information and Communications Technology, Kobe, Hyogo 651-2492 Japan

Correspondence to Hidekazu Tanaka: htanaka{at}pharma1.med.osaka-u.ac.jp

Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone.

K. Okamura and H. Tanaka contributed equally to this work.

Abbreviations used in this paper: CCD, charge-coupled imaging device; DIV, day in vitro; SCCL, spine cotyloid curve length; W2A-cadherin, W2A mutant of N-cadherin.


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