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PMID: 16330714 Published · ppublish English Journal Article

The Rac activator Tiam1 is required for (alpha)3(beta)1-mediated laminin-5 deposition, cell spreading, and cell migration.

The Journal of cell biology ·Vol. 171 ·No. 5 ·2005-12-05 ·Pages 871-81

Hamelers IH, Olivo C, Mertens AE, Pegtel DM, van der Kammen RA, Sonnenberg A, Collard JG

Abstract

The Rho-like guanosine triphosphatase Rac1 regulates various signaling pathways, including integrin-mediated adhesion and migration of cells. However, the mechanisms by which integrins signal toward Rac are poorly understood. We show that the Rac-specific guanine nucleotide exchange factor Tiam1 (T-lymphoma invasion and metastasis 1) is required for the integrin-mediated laminin (LN)-5 deposition, spreading, and migration of keratinocytes. In contrast to wild-type keratinocytes, Tiam1-deficient (Tiam1-/-) keratinocytes are unable to adhere to and spread on a glass substrate because they are unable to deposit their own LN5 substrate. Both Tiam1 and V12Rac1 can rescue the defects of Tiam1-/- keratinocytes, indicating that these deficiencies are caused by impaired Tiam1-mediated Rac activation. Tiam1-/- cells are unable to activate Rac upon alpha3beta1-mediated adhesion to an exogenous LN5 substrate. Moreover, Tiam1 deficiency impairs keratinocyte migration in vitro and reepithelialization of excision wounds in mouse skin. Our studies indicate that Tiam1 is a key molecule in alpha3beta1-mediated activation of Rac, which is essential for proper production and secretion of LN5, a requirement for the spreading and migration of keratinocytes.

MeSH Terms
Animals Cell Adhesion Cell Adhesion Molecules/metabolism Cell Movement Cell Shape Cells, Cultured Collagen Type IV/metabolism Guanine Nucleotide Exchange Factors/genetics,physiology Integrin alpha3beta1/physiology Keratinocytes/physiology Mice Mutation Neoplasm Proteins/genetics,physiology Signal Transduction Skin/cytology,metabolism T-Lymphoma Invasion and Metastasis-inducing Protein 1 Wound Healing rac1 GTP-Binding Protein/metabolism
Chemicals
Cell Adhesion Molecules Collagen Type IV Guanine Nucleotide Exchange Factors Integrin alpha3beta1 Neoplasm Proteins T-Lymphoma Invasion and Metastasis-inducing Protein 1 Tiam1 protein, mouse kalinin rac1 GTP-Binding Protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hamelers Irene H L
Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Olivo Cristina
Mertens Alexander E E
Pegtel D Michiel
van der Kammen Rob A
Sonnenberg Arnoud
Collard John G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200509172
Published
2005-12-05
Pages
871-81
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171282
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200509172 PMC Full Text View journal details
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