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Vol. 12, Issue 10, 3126-3138, October 2001

Cross Talk between ₁ and _V Integrins: ₁ Affects ₃ mRNA Stability

Saverio Francesco Retta,^* Georgia Cassarà, Monica D'Amato, Riccardo Alessandro, Maurizio Pellegrino,^* Simona Degani,^* Giacomo De Leo, Lorenzo Silengo,^* and Guido Tarone^*

 ^*Department of Genetics, Biology, and Biochemistry, University of Torino, 10126 Torino, Italy; and  Department of Biopatologia e Metodologie Biomediche, University of Palermo, 90133 Palermo, Italy

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 ₁-null GD25 cells ectopically expressing the ₁A integrin subunit, we provide evidence for the existence of a cross talk between ₁ and _V integrins that affects the ratio of _V3 and _V5 integrin cell surface levels. In particular, we demonstrate that a down-regulation of _V3 and an up-regulation of _V5 occur as a consequence of ₁A expression. Moreover, with the use of GD25 cells expressing the integrin isoforms ₁B and ₁D, as well as two ₁ cytoplasmic domain deletion mutants lacking either the entire cytoplasmic domain (₁TR) or only its "variable" region (₁COM), we show that the effects of ₁ over _V integrins take place irrespective of the type of ₁ isoform, but require the presence of the "common" region of the ₁ cytoplasmic domain. In an attempt to establish the regulatory mechanism(s) whereby ₁ integrins exert their trans-acting functions, we have found that the down-regulation of _V3 is due to a decreased ₃ subunit mRNA stability, whereas the up-regulation of _V5 is 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.

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Corresponding author. E-mail address: francesco.retta{at}unito.it.

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Molecular Biology of the Cell
Vol. 12, 3126-3138, October 2001
Copyright © 2001 by The American Society for Cell Biology

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