The role of alpha 4 beta 1 integrin in cell motility and fibronectin matrix assembly.
The alpha 4 beta 1 integrin has been suggested to play important roles in embryogenesis and pathogenesis of many diseases which involve both cell adhesion and cell migration. Previous studies using anti-alpha 4 beta 1 antibodies and fibronectin (Fn) fragments have suggested that alpha 4 beta 1 integrins may be involved in cell motility on Fn and vascular cell adhesion molecule-1 (VCAM-1). However, the cells used in these studies also express other Fn integrin receptors including alpha 5 beta 1 integrin, which is known to function in cell motility on Fn. To test whether alpha 4 beta 1 integrins mediate cell motility on Fn and VCAM-1 in the absence of alpha 5 beta 1 integrin, we expressed human alpha 4 integrin in a Chinese hamster ovary (CHO) cell line that is deficient in alpha 5 beta 1 integrin (CHO B2). The parental alpha 5 deficient CHO B2 cells were unable to adhere, spread or migrate on Fn, nor could they assemble a fibrillar Fn matrix. Expression of alpha 4 beta 1 integrin in the CHO B2 cells enabled the cells to adhere, spread and migrate on Fn and on VCAM-1 but not to assemble a fibrillar Fn matrix. The cellular processes mediated by the interaction of alpha 4 beta 1 with Fn or VCAM-1 were inhibited by the CS1 peptide derived from the major alpha 4 beta 1 binding site on Fn. These findings demonstrate that alpha 4 beta 1 integrins not only function as cell adhesion receptors but also as cell motility receptors for Fn and VCAM-1 independent of alpha 5 beta 1. Moreover, they reveal important functional differences between Fn binding integrins. The alpha 4-positive, alpha 5-negative CHO cells described in this report will be useful tools in studying the mechanism of molecular signalling during integrin mediated cellular processes.
Wu
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C
Samule C. Johnson Medical Research Center, Mayo Clinic Scottsdale, AZ 85259, USA.
Fields
A J
AJ
Kapteijn
B A
BA
McDonald
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D008969:Molecular Sequence Data; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1