Distinct cellular functions mediated by different VLA integrin alpha subunit cytoplasmic domains.
To characterize VLA alpha subunit cytoplasmic domain functions, unaltered alpha 2 cDNA (called X2C2) and two chimeric cDNAs (called X2C5 and X2C4) were constructed with extracellular alpha 2 domains and cytoplasmic alpha 2, alpha 5, and alpha 4 domains respectively. Upon transfection into rhabdomyosarcoma (RD) cells, each construct yielded comparable expression levels, immunoprecipitation profiles, and avidity for collagen and laminin. However, while RDX2C2 and RDX2C5 transfectants mediated collagen gel contraction, RDX2C4 and a mock transfectant (RDpF) did not. Conversely, only RDX2C4 cells (but not RDX2C2 or RDX2C5) showed enhanced cell migration on collagen and laminin compared with RDpF cells. This indicates markedly differing roles for integrin alpha subunit cytoplasmic domains in post-ligand binding events. Furthermore, stable exertion of physical force (collagen gel contraction) may involve fundamentally different cellular machinery than the transient adhesion occurring during cell migration. Finally, these findings provide insight into a functional flexibility perhaps resulting from multiple integrins binding to identical ligands.
Chan
B M
BM
Tumor Virology Division, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Kassner
P D
PD
Schiro
J A
JA
Byers
H R
HR
Kupper
T S
TS
Hemler
M E
ME
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003094:Collagen / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D016023:Integrins / Q000737:chemistry*; D007797:Laminin / Q000737:chemistry; D008969:Molecular Sequence Data; D014162:Transfection
D005353:Fibronectins; D005782:Gels; D016023:Integrins; D007797:Laminin; D003094:Collagen