This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Echarri, A.
Right arrow Articles by Pendergast, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Echarri, A.
Right arrow Articles by Pendergast, A. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2004, p. 4979-4993, Vol. 24, No. 11
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.11.4979-4993.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Abl Interactor 1 (Abi-1) Wave-Binding and SNARE Domains Regulate Its Nucleocytoplasmic Shuttling, Lamellipodium Localization, and Wave-1 Levels

Asier Echarri,1 Margaret J. Lai,2 Matthew R. Robinson,1 and Ann Marie Pendergast1*

Department of Pharmacology and Cancer Biology,1 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Duke University, Durham, North Carolina 277102

Received 21 December 2003/ Returned for modification 21 January 2004/ Accepted 6 March 2004

The Abl interactor 1 (Abi-1) protein has been implicated in the regulation of actin dynamics and localizes to the tips of lamellipodia and filopodia. Here, we show that Abi-1 binds the actin nucleator protein Wave-1 through an amino-terminal Wave-binding (WAB) domain and that disruption of the Abi-1-Wave-1 interaction prevents Abi-1 from reaching the tip of the lamellipodium. Abi-1 binds to the Wave homology domain of Wave-1, a region that is required for translocation of Wave-1 to the lamellipodium. Mouse embryo fibroblasts that lack one allele of Abi-1 and are homozygous null for the related Abi-2 protein exhibit decreased Wave-1 protein levels. This phenotype is rescued by Abi-1 proteins that retain Wave-1 binding but not by Abi-1 mutants that cannot bind to Wave-1. Moreover, we uncovered an overlapping SNARE domain in the amino terminus of Abi-1 that interacts with Syntaxin-1, a SNARE family member. Further, we demonstrated that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent manner and that complete nuclear translocation of Abi-1 in the absence of LMB requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1. Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading edge to regulate Wave-1 localization and protein levels.

* Corresponding author. Mailing address: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Duke University, Durham, NC 27710. Phone: (919) 681-8086. Fax: (919) 681-7148. E-mail: pende014{at}mc.duke.edu.

Molecular and Cellular Biology, June 2004, p. 4979-4993, Vol. 24, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.11.4979-4993.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ryu, J. R., Echarri, A., Li, R., Pendergast, A. M. (2009). Regulation of Cell-Cell Adhesion by Abi/Diaphanous Complexes. Mol. Cell. Biol. 29: 1735-1748 [Abstract] [Full Text]  
  • Schmidt, K. L., Marcus-Gueret, N., Adeleye, A., Webber, J., Baillie, D., Stringham, E. G. (2009). The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1. Development 136: 563-574 [Abstract] [Full Text]  
  • Wang, H., Patel, V., Miyazaki, H., Gutkind, J.S., Yeudall, W.A. (2009). Role for EPS8 in squamous carcinogenesis. Carcinogenesis 30: 165-174 [Abstract] [Full Text]  
  • Yu, W., Sun, X., Clough, N., Cobos, E., Tao, Y., Dai, Z. (2008). Abi1 gene silencing by short hairpin RNA impairs Bcr-Abl-induced cell adhesion and migration in vitro and leukemogenesis in vivo. Carcinogenesis 29: 1717-1724 [Abstract] [Full Text]  
  • Huang, C.-H., Lin, T.-Y., Pan, R.-L., Juang, J.-L. (2007). The Involvement of Abl and PTP61F in the Regulation of Abi Protein Localization and Stability and Lamella Formation in Drosophila S2 Cells. J. Biol. Chem. 282: 32442-32452 [Abstract] [Full Text]  
  • Wang, C., Navab, R., Iakovlev, V., Leng, Y., Zhang, J., Tsao, M.-S., Siminovitch, K., McCready, D. R., Done, S. J. (2007). Abelson Interactor Protein-1 Positively Regulates Breast Cancer Cell Proliferation, Migration, and Invasion. Mol Cancer Res 5: 1031-1039 [Abstract] [Full Text]  
  • Sossey-Alaoui, K., Li, X., Cowell, J. K. (2007). c-Abl-mediated Phosphorylation of WAVE3 Is Required for Lamellipodia Formation and Cell Migration. J. Biol. Chem. 282: 26257-26265 [Abstract] [Full Text]  
  • Caracino, D., Jones, C., Compton, M., Saxe, C. L. III (2007). The N-Terminus of Dictyostelium Scar Interacts with Abi and HSPC300 and Is Essential for Proper Regulation and Function. Mol. Biol. Cell 18: 1609-1620 [Abstract] [Full Text]  
  • Stuart, J. R., Gonzalez, F. H., Kawai, H., Yuan, Z.-M. (2006). c-Abl Interacts with the WAVE2 Signaling Complex to Induce Membrane Ruffling and Cell Spreading. J. Biol. Chem. 281: 31290-31297 [Abstract] [Full Text]  
  • Rakeman, A. S., Anderson, K. V. (2006). Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching. Development 133: 3075-3083 [Abstract] [Full Text]  
  • Luo, X., Levens, E., Williams, R. S., Chegini, N. (2006). The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-beta. Hum Reprod 21: 1380-1386 [Abstract] [Full Text]  
  • Suetsugu, S., Kurisu, S., Oikawa, T., Yamazaki, D., Oda, A., Takenawa, T. (2006). Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP3, and Rac. JCB 173: 571-585 [Abstract] [Full Text]  
  • Mitsushima, M., Sezaki, T., Akahane, R., Ueda, K., Suetsugu, S., Takenawa, T., Kioka, N. (2006). Protein kinase A-dependent increase in WAVE2 expression induced by the focal adhesion protein vinexin. GENES CELLS 11: 281-292 [Abstract] [Full Text]  
  • Sossey-Alaoui, K., Li, X., Ranalli, T. A., Cowell, J. K. (2005). WAVE3-mediated Cell Migration and Lamellipodia Formation Are Regulated Downstream of Phosphatidylinositol 3-Kinase. J. Biol. Chem. 280: 21748-21755 [Abstract] [Full Text]  
  • Basu, D., Le, J., El-Essal, S. E.-D., Huang, S., Zhang, C., Mallery, E. L., Koliantz, G., Staiger, C. J., Szymanski, D. B. (2005). DISTORTED3/SCAR2 Is a Putative Arabidopsis WAVE Complex Subunit That Activates the Arp2/3 Complex and Is Required for Epidermal Morphogenesis. Plant Cell 17: 502-524 [Abstract] [Full Text]  
  • Grove, M., Demyanenko, G., Echarri, A., Zipfel, P. A., Quiroz, M. E., Rodriguiz, R. M., Playford, M., Martensen, S. A., Robinson, M. R., Wetsel, W. C., Maness, P. F., Pendergast, A. M. (2004). Abi2-Deficient Mice Exhibit Defective Cell Migration, Aberrant Dendritic Spine Morphogenesis, and Deficits in Learning and Memory. Mol. Cell. Biol. 24: 10905-10922 [Abstract] [Full Text]  
  • Bompard, G., Caron, E. (2004). Regulation of WASP/WAVE proteins: making a long story short. JCB 166: 957-962 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»