![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on September 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 17, 2001
Revised on May 30, 2002
Accepted on June 20, 2002
4ß1 integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism
1 Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205
* Corresponding author. E-mail address: jyang{at}jhmi.edu.
4ß1 integrin plays an important role in cell migration. We show that, when ectopically expressed in CHO cells, 4ß1 is sufficient and required for promoting protrusion of broad lamellipodia in response to scratch-wounding, whereas 5ß1 does not have this effect. By time-lapse microscopy of cells expressing an 4/GFP fusion protein, we show that 4ß1 forms transient puncta at the leading edge of cells that begin to protrude lamellipodia in response to scratch-wounding. The cells expressing a mutant 4/GFP that binds paxillin at a reduced level had a faster response to scratch-wounding, forming 4-positive puncta and protruding lamellipodia much earlier. While enhancing lamellipodia protrusion, this mutation reduces random motility of the cells in transwell assays, indicating that lamellipodia protrusion and random motility are distinct types of motile activities that are differentially regulated by interactions between 4ß1 and paxillin. Finally, we show that, at the leading edge, 4-positive puncta and paxillin-positive focal complexes/adhesions do not colocalize, but 4ß1 and paxillin colocalize partially in ruffles. These findings provide evidence for a specific role of 4ß1 in lamellipodia protrusion that is distinct from the motility-promoting functions of 5ß1 and other integrins that mediate cell adhesion and signaling events through focal complexes and focal adhesions.
This article has been cited by other articles:
|
|
 |
|
  D. A. Dikeman, L. A. Rivera Rosado, T. A. Horn, C. S. Alves, K. Konstantopoulos, and J. T. Yang {alpha}4{beta}1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation Am J Physiol Cell Physiol, July 1, 2008; 295(1): C151 - C159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Escribese, E. Conde, D. Saenz-Morales, P. L. Hordijk, and M. L. Garcia-Bermejo Mononuclear Cell Extravasation in an Inflammatory Response Is Abrogated by All-Trans-Retinoic Acid through Inhibiting the Acquisition of an Appropriate Migratory Phenotype J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 454 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xi, G. Nakajima, T. Hamil, O. Fodstad, A. Riker, and J. Ju Association of insulin-like growth factor binding protein-3 expression with melanoma progression Mol. Cancer Ther., December 1, 2006; 5(12): 3078 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Hsia, S.-T. Lim, J. A. Bernard-Trifilo, S. K. Mitra, S. Tanaka, J. den Hertog, D. N. Streblow, D. Ilic, M. H. Ginsberg, and D. D. Schlaepfer Integrin {alpha}4{beta}1 Promotes Focal Adhesion Kinase-Independent Cell Motility via {alpha}4 Cytoplasmic Domain-Specific Activation of c-Src Mol. Cell. Biol., November 1, 2005; 25(21): 9700 - 9712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, L. C. Bridges, and J. M. White Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family Members Mol. Biol. Cell, October 1, 2005; 16(10): 4982 - 4991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Choma, K. Pumiglia, and C. M. DiPersio Integrin {alpha}3{beta}1 directs the stabilization of a polarized lamellipodium in epithelial cells through activation of Rac1 J. Cell Sci., August 1, 2004; 117(17): 3947 - 3959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Keese, J. Wegener, S. R. Walker, and I. Giaever Electrical wound-healing assay for cells in vitro PNAS, February 10, 2004; 101(6): 1554 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Watters Video Views and Reviews CBE Life Sci Educ, December 1, 2003; 2(4): 210 - 213. [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Goldfinger, J. Han, W. B. Kiosses, A. K. Howe, and M. H. Ginsberg Spatial restriction of {alpha}4 integrin phosphorylation regulates lamellipodial stability and {alpha}4{beta}1-dependent cell migration J. Cell Biol., August 18, 2003; 162(4): 731 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Spessotto, M. Cervi, M. T. Mucignat, G. Mungiguerra, I. Sartoretto, R. Doliana, and A. Colombatti beta 1 Integrin-dependent Cell Adhesion to EMILIN-1 Is Mediated by the gC1q Domain J. Biol. Chem., February 14, 2003; 278(8): 6160 - 6167. [Abstract] [Full Text] [PDF]
|
|
