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Published online July 21, 2008
doi:10.1083/jcb.200802069
The Journal of Cell Biology
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Nakao et al.
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ARTICLE

 Contact-dependent promotion of cell migration by the OL-protocadherin–Nap1 interaction

Shinsuke Nakao1,2, Anna Platek2, Shinji Hirano2, and Masatoshi Takeichi2

1 Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
2 RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan

Correspondence to Shinji Hirano: s-hirano{at}cdb.riken.jp; or Masatoshi Takeichi: takeichi{at}cdb.riken.jp

OL-protocadherin (OL-pc) is a transmembrane protein belonging to the cadherin superfamily, which has been shown to accumulate at cell–cell contacts via its homophilic interaction, but its molecular roles remain elusive. In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly. In astrocytoma U251 cells not expressing OL-pc, Nap1 was localized only along the lamellipodia. However, exogenous expression of OL-pc in these cells recruited Nap1 as well as WAVE1 to cell–cell contact sites. Although OL-pc expression had no effect on the motility of solitary U251 cells, it accelerated their movement when they were in contact with one another, causing concomitant reorganization of F-actin and N-cadherin at cell junctions. OL-pc mutants lacking the Nap1-binding site exhibited no such effect. N-cadherin knockdown mimicked OL-pc expression in enhancing cell movement. These results suggest that OL-pc remodels the motility and adhesion machinery at cell junctions by recruiting the Nap1–WAVE1 complex to these sites and, in turn, promotes the migration of cells.

Abbreviations used in this paper: Abi, Abl interactor; Arp, actin-related protein; CYFIP, cytoplasmic interacting FMR1 protein; Nap1, Nck-associated protein 1; NBS, Nap1-binding site; OL-pc, OL-protocadherin.

© 2008 Nakao et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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