MCP Waters-The Science of What's Possible
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/mcp.M600050-MCP200 on May 30, 2006.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
Right arrow All Versions of this Article:
M600050-MCP200v1
5/8/1437    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Related articles in MCP
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Glossary
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fang, Z.
Right arrow Articles by Yao, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fang, Z.
Right arrow Articles by Yao, X.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Molecular & Cellular Proteomics 5:1437-1449, 2006.
© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Proteomic Identification and Functional Characterization of a Novel ARF6 GTPase-activating Protein, ACAP4*,S

Zhiyou Fang{ddagger},§, Yong Miao{ddagger},§, Xia Ding,||||, Hui Deng{ddagger}, Siqi Liu{ddagger}, Fengsong Wang{ddagger},¶, Rihong Zhou||, Charles Watson||, Chuanhai Fu{ddagger},¶, Qicong Hu{ddagger}, James W. Lillard, Jr**, Michael Powell**, Yong Chen{ddagger}{ddagger},§§, John G. Forte|| and Xuebiao Yao{ddagger},¶,¶¶

From the {ddagger} Laboratory of Cellular Dynamics, Hefei National Laboratory for Physical Sciences at Microscale and University of Science and Technology of China, Hefei 230027, China, Departments of Physiology and ** Biochemistry, Morehouse School of Medicine, Atlanta, Georgia 30310, || Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, {ddagger}{ddagger} Department of Hepatology, Xi’jing Hospital, The Fourth Military Medical University, Xi’an 710032, China, and |||| Department of Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

ARF6 GTPase is a conserved regulator of membrane trafficking and actin-based cytoskeleton dynamics at the leading edge of migrating cells. A key determinant of ARF6 function is the lifetime of the GTP-bound active state, which is orchestrated by GTPase-activating protein (GAP) and GTP-GDP exchanging factor. However, very little is known about the molecular mechanisms underlying ARF6-mediated cell migration. To systematically analyze proteins that regulate ARF6 activity during cell migration, we performed a proteomic analysis of proteins selectively bound to active ARF6 using mass spectrometry and identified a novel ARF6-specific GAP, ACAP4. ACAP4 encodes 903 amino acids and contains two coiled coils, one pleckstrin homology domain, one GAP motif, and two ankyrin repeats. Our biochemical characterization demonstrated that ACAP4 has a phosphatidylinositol 4,5-bisphosphate-dependent GAP activity specific for ARF6. The co-localization of ACAP4 with ARF6 occurred in ruffling membranes formed upon AIF4 and epidermal growth factor stimulation. ACAP4 overexpression limited the recruitment of ARF6 to the membrane ruffles in the absence of epidermal growth factor stimulation. Expression of GTP hydrolysis-resistant ARF6Q67L resulted in accumulations of ACAP4 and ARF6 in the cytoplasmic membrane, suggesting that GTP hydrolysis is required for the ARF6-dependent membrane remodeling. Significantly the depletion of ACAP4 by small interfering RNA or inhibition of ARF6 GTP hydrolysis by overexpressing GAP-deficient ACAP4 suppressed ARF6-dependent cell migration in wound healing, demonstrating the importance of ACAP4 in cell migration. Thus, our study sheds new light on the biological function of ARF6-mediated cell migration.

§§ To whom correspondence may be addressed. E-mail: gdwkcy{at}fmmu.edu.cn

¶¶ A Georgia Cancer Coalition Eminent Cancer Scholar. To whom correspondence may be addressed. E-mail: yaoxb{at}ustc.edu.cn or xyao{at}msm.edu


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related articles in MCP:

Additions & Corrections

MCP 2006 5: 1718. [Full Text]  



This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
F. Wang, P. Xia, F. Wu, D. Wang, W. Wang, T. Ward, Y. Liu, F. Aikhionbare, Z. Guo, M. Powell, et al.
Helicobacter pylori VacA Disrupts Apical Membrane-Cytoskeletal Interactions in Gastric Parietal Cells
J. Biol. Chem., September 26, 2008; 283(39): 26714 - 26725.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. L. Ha, S. Bharti, H. Inoue, W. C. Vass, F. Campa, Z. Nie, A. de Gramont, Y. Ward, and P. A. Randazzo
ASAP3 Is a Focal Adhesion-associated Arf GAP That Functions in Cell Migration and Invasion
J. Biol. Chem., May 30, 2008; 283(22): 14915 - 14926.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. Cotton, P.-L. Boulay, T. Houndolo, N. Vitale, J. A. Pitcher, and A. Claing
Endogenous ARF6 Interacts with Rac1 upon Angiotensin II Stimulation to Regulate Membrane Ruffling and Cell Migration
Mol. Biol. Cell, February 1, 2007; 18(2): 501 - 511.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.