HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takahashi, M. Articles by Takai, Y. Search for Related Content PubMed Articles by Takahashi, M. Articles by Takai, Y.

¹ Department of Biochemistry and Molecular Biology, Division of Molecular and Cellular Biology, and ² Department of Internal Medicine, Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
³ Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan

Moving cells form protrusions, such as filopodia and lamellipodia, and focal complexes at leading edges, which eventually enhance cell movement. The Rho family small G proteins, Rac1, Cdc42 and RhoA, are involved in the formation of these leading edge structures. We investigated the role of another small G protein Rap1 in the platelet-derived growth factor (PDGF)-induced formation of leading edge structures and cell movement. Upon stimulation of NIH3T3 cells by PDGF, leading edge structures were formed and Necl-5, integrin _Vβ₃, and PDGF receptor were accumulated at leading edges. Rap1, upstream regulators of Rap1 such as Crk and C3G, and a downstream effector RalGDS, were accumulated at peripheral ruffles over lamellipodia. Over-expression of Rap1GAP, which inactivates Rap1, and knockdown of Rap1 inhibited the PDGF-induced formation of leading edge structures, accumulation of these molecules, and cell movement. In addition, Rap1 activation subsequently induced accumulation of Rac1, Vav2 and PAK at peripheral ruffles, which was inhibited by Rap1GAP and knockdown of Rap1. These results indicate that Rap1, activated by PDGF, is recruited to leading edges and that Rac1 is thereby activated locally at peripheral ruffles. This process is pivotal for the PDGF-induced formation of leading edge structures and cell movement.

^* Correspondence: Email: ytakai{at}med.kobe-u.ac.jp

This article has been cited by other articles:

				M. Miyata, H. Ogita, H. Komura, S. Nakata, R. Okamoto, M. Ozaki, T. Majima, N. Matsuzawa, S. Kawano, A. Minami, et al. Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor J. Cell Sci., December 1, 2009; 122(23): 4319 - 4329. [Abstract] [Full Text] [PDF]

				M. Miyata, Y. Rikitake, M. Takahashi, Y. Nagamatsu, Y. Yamauchi, H. Ogita, K.-i. Hirata, and Y. Takai Regulation by Afadin of Cyclical Activation and Inactivation of Rap1, Rac1, and RhoA Small G Proteins at Leading Edges of Moving NIH3T3 Cells J. Biol. Chem., September 4, 2009; 284(36): 24595 - 24609. [Abstract] [Full Text] [PDF]

				W. J. Nelson Remodeling epithelial cell organization: transitions between front-rear and apical-Basal polarity. Cold Spring Harb Perspect Biol, July 1, 2009; 1(1): a000513 - a000513. [Abstract] [Full Text] [PDF]