The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 2 Mar 2004
doi: 10.1242/jcs.01003
Research Article
Laminin 5 deposition regulates keratinocyte polarization and persistent migration
Diane E. Frank*
and
William G. Carter
* Author for correspondence (e-mail: difrank{at}fhcrc.org)
Repair of wounded epidermis requires both keratinocyte migration and deposition of laminin 5 over exposed dermal collagen. To understand the coupling between leading cell migration and laminin 5 deposition, we developed a novel migration assay using time-lapse microscopy. We demonstrate that in migrating, human keratinocytes the deposition of laminin 5 promoted 'processive migration', characterized by stable cell polarization that was tightly coupled to persistent, linear migration in the absence of a chemotactic gradient. Processive migration required deposition of laminin 5, which was restricted to the rear of the polar cell. Integrin 
3
1 interacted with these laminin 5 deposits at contact sites that did not require actin-dependent cross-linking. Further, we show that the migrating cells switched adhesion by integrin 21 on collagen at the front of the cell to integrin 31 on exogenous laminin 5 at the rear of the cell. Along with this switch of integrin usage was the removal of collagen from sites under the cell that precisely correlated with deposition of laminin 5. Processive migration was blocked with suppressors of microtubule dynamics (nocodazole and taxol) or rottlerin, a PKC-
inhibitor. These drugs were also shown to block deposition of laminin 5 but, surprisingly, constitutive secretion was unimpaired, suggesting deposition was a regulated event. Thus, at the front of the cell, the leading lamellipodium was stabilized through integrin interactions in focal complexes with the exogenous substratum. However, at the rear of the cell, stable cell polarization and linear migration was promoted by laminin 5 deposits and integrin 31.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Has, C. Herz, E. Zimina, H.-Y. Qu, Y. He, Z.-G. Zhang, T.-T. Wen, Y. Gache, M. Aumailley, and L. Bruckner-Tuderman
Kindlin-1 Is Required for RhoGTPase-Mediated Lamellipodia Formation in Keratinocytes
Am. J. Pathol.,
October 1, 2009;
175(4):
1442 - 1452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Mitchell, C. Szekeres, V. Milano, K. B. Svenson, M. Nilsen-Hamilton, J. A. Kreidberg, and C. M. DiPersio
{alpha}3{beta}1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3
J. Cell Sci.,
June 1, 2009;
122(11):
1778 - 1787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Underwood, W. G. Carter, M. L. Usui, and J. E. Olerud
Ultrastructural Localization of Integrin Subunits {beta}4 and {alpha}3 Within the Migrating Epithelial Tongue of In Vivo Human Wounds
J. Histochem. Cytochem.,
February 1, 2009;
57(2):
123 - 142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Margadant, K. Raymond, M. Kreft, N. Sachs, H. Janssen, and A. Sonnenberg
Integrin {alpha}3{beta}1 inhibits directional migration and wound re-epithelialization in the skin
J. Cell Sci.,
January 15, 2009;
122(2):
278 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D'Alessio, L. Gerasi, and F. Blasi
uPAR-deficient mouse keratinocytes fail to produce EGFR-dependent laminin-5, affecting migration in vivo and in vitro
J. Cell Sci.,
December 1, 2008;
121(23):
3922 - 3932.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Lamar, K. M. Pumiglia, and C. M. DiPersio
An Immortalization-Dependent Switch in Integrin Function Up-regulates MMP-9 to Enhance Tumor Cell Invasion
Cancer Res.,
September 15, 2008;
68(18):
7371 - 7379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Fafet, C. Rebouissou, T. Maudelonde, and M.-L. Vignais
Opposite Effects of Transforming Growth Factor-{beta} Activation and Rho-Associated Kinase Inhibition on Human Trophoblast Migration in a Reconstituted Placental-Endometrial Coculture System
Endocrinology,
September 1, 2008;
149(9):
4475 - 4485.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-A. Nakrieko, I. Welch, H. Dupuis, D. Bryce, A. Pajak, R. St. Arnaud, S. Dedhar, S. J. A. D'Souza, and L. Dagnino
Impaired Hair Follicle Morphogenesis and Polarized Keratinocyte Movement upon Conditional Inactivation of Integrin-linked Kinase in the Epidermis
Mol. Biol. Cell,
April 1, 2008;
19(4):
1462 - 1473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kligys, J. N. Claiborne, P. J. DeBiase, S. B. Hopkinson, Y. Wu, K. Mizuno, and J. C. R. Jones
The Slingshot Family of Phosphatases Mediates Rac1 Regulation of Cofilin Phosphorylation, Laminin-332 Organization, and Motility Behavior of Keratinocytes
J. Biol. Chem.,
November 2, 2007;
282(44):
32520 - 32528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Stepp, Y. Liu, S. Pal-Ghosh, R. A. Jurjus, G. Tadvalkar, A. Sekaran, K. LoSicco, L. Jiang, M. Larsen, L. Li, et al.
Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1
J. Cell Sci.,
August 15, 2007;
120(16):
2851 - 2863.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. DiPersio
Double Duty for Rac1 in Epidermal Wound Healing
Sci. Signal.,
June 19, 2007;
2007(391):
pe33 - pe33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Sugawara, D. Tsuruta, H. Kobayashi, K. Ikeda, S. B. Hopkinson, J. C.R. Jones, and M. Ishii
Spatial and Temporal Control of Laminin-332 (5) and -511 (10) Expression During Induction of Anagen Hair Growth
J. Histochem. Cytochem.,
January 1, 2007;
55(1):
43 - 55.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Herz, M. Aumailley, C. Schulte, U. Schlotzer-Schrehardt, L. Bruckner-Tuderman, and C. Has
Kindlin-1 Is a Phosphoprotein Involved in Regulation of Polarity, Proliferation, and Motility of Epidermal Keratinocytes
J. Biol. Chem.,
November 24, 2006;
281(47):
36082 - 36090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. U. Sehgal, P. J. DeBiase, S. Matzno, T.-L. Chew, J. N. Claiborne, S. B. Hopkinson, A. Russell, M. P. Marinkovich, and J. C. R. Jones
Integrin beta4 Regulates Migratory Behavior of Keratinocytes by Determining Laminin-332 Organization
J. Biol. Chem.,
November 17, 2006;
281(46):
35487 - 35498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Pullar, B. S. Baier, Y. Kariya, A. J. Russell, B. A.J. Horst, M. P. Marinkovich, and R. R. Isseroff
beta4 Integrin and Epidermal Growth Factor Coordinately Regulate Electric Field-mediated Directional Migration via Rac1
Mol. Biol. Cell,
November 1, 2006;
17(11):
4925 - 4935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Z. Mak, G. M. Kavanaugh, M. M. Buschmann, S. M. Stickley, M. Koch, K. H. Goss, H. Waechter, A. Zuk, and K. S. Matlin
Regulated Synthesis and Functions of Laminin 5 in Polarized Madin-Darby Canine Kidney Epithelial Cells
Mol. Biol. Cell,
August 1, 2006;
17(8):
3664 - 3677.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Pullar, A. Rizzo, and R. R. Isseroff
beta-Adrenergic Receptor Antagonists Accelerate Skin Wound Healing: EVIDENCE FOR A CATECHOLAMINE SYNTHESIS NETWORK IN THE EPIDERMIS
J. Biol. Chem.,
July 28, 2006;
281(30):
21225 - 21235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Natarajan, J. D. Omobono II, Z. Guo, S. Hopkinson, A. J.F. Lazar, T. Brenn, J. C. Jones, and J. G. Rheinwald
A Keratinocyte Hypermotility/Growth-Arrest Response Involving Laminin 5 and p16INK4A Activated in Wound Healing and Senescence
Am. J. Pathol.,
June 1, 2006;
168(6):
1821 - 1837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Wilhelmsen, S. H.M. Litjens, and A. Sonnenberg
Multiple Functions of the Integrin {alpha}6{beta}4 in Epidermal Homeostasis and Tumorigenesis
Mol. Cell. Biol.,
April 15, 2006;
26(8):
2877 - 2886.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Pullar, J. C. Grahn, W. Liu, and R. R. Isseroff
{beta}2-Adrenergic receptor activation delays wound healing
FASEB J,
January 1, 2006;
20(1):
76 - 86.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. G. Harper, S. M. Alvares, and W. G. Carter
Wounding activates p38 map kinase and activation transcription factor 3 in leading keratinocytes
J. Cell Sci.,
August 1, 2005;
118(15):
3471 - 3485.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Tsubota, C. Yasuda, Y. Kariya, T. Ogawa, T. Hirosaki, H. Mizushima, and K. Miyazaki
Regulation of Biological Activity and Matrix Assembly of Laminin-5 by COOH-terminal, LG4-5 Domain of {alpha}3 Chain
J. Biol. Chem.,
April 15, 2005;
280(15):
14370 - 14377.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Iyer, K. Pumiglia, and C. M. DiPersio
{alpha}3{beta}1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression
J. Cell Sci.,
March 15, 2005;
118(6):
1185 - 1195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Krampert, W. Bloch, T. Sasaki, P. Bugnon, T. Rulicke, E. Wolf, M. Aumailley, W. C. Parks, and S. Werner
Activities of the Matrix Metalloproteinase Stromelysin-2 (MMP-10) in Matrix Degradation and Keratinocyte Organization in Wounded Skin
Mol. Biol. Cell,
December 1, 2004;
15(12):
5242 - 5254.
[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]
|
|
|
© The Company of Biologists Ltd 2004
