6533b7d7fe1ef96bd12678f9

RESEARCH PRODUCT

Cross Talk between β1and αVIntegrins: β1Affects β3mRNA Stability

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There is increasing evidence that a fine-tuned integrin cross talk can generate a high degree of specificity in cell adhesion, suggesting that spatially and temporally coordinated expression and activation of integrins are more important for regulated cell adhesive functions than the intrinsic specificity of individual receptors. However, little is known concerning the molecular mechanisms of integrin cross talk. With the use of β1-null GD25 cells ectopically expressing the β1A integrin subunit, we provide evidence for the existence of a cross talk between β1and αVintegrins that affects the ratio of αVβ3and αVβ5integrin cell surface levels. In particular, we demonstrate that a down-regulation of αVβ3and an up-regulation of αVβ5occur as a consequence of β1A expression. Moreover, with the use of GD25 cells expressing the integrin isoforms β1B and β1D, as well as two β1cytoplasmic domain deletion mutants lacking either the entire cytoplasmic domain (β1TR) or only its “variable” region (β1COM), we show that the effects of β1over αVintegrins take place irrespective of the type of β1isoform, but require the presence of the “common” region of the β1cytoplasmic domain. In an attempt to establish the regulatory mechanism(s) whereby β1integrins exert theirtrans-acting functions, we have found that the down-regulation of αVβ3is due to a decreased β3subunit mRNA stability, whereas the up-regulation of αVβ5is mainly due to translational or posttranslational events. These findings provide the first evidence for an integrin cross talk based on the regulation of mRNA stability.