Functional comparison of the alpha3A and alpha3B cytoplasmic domain variants of the chicken alpha3 integrin subunit.

Integrin alpha3beta1 can be alternatively spliced to generate alpha3A and alpha3B cytoplasmic domain variants that are conserved among vertebrates. To identify distinct functions of these variants, we transfected cells with intact alpha3 integrins or chimeric receptors. alpha3Abeta1 and alpha3Bbeta1 each localized to focal contacts in keratinocytes on an extracellular matrix rich in laminin-5, to which both are known to bind with high affinity. However, alpha3B accumulated intracellularly in keratinocytes on collagen, suggesting that laminin binding may stabilize alpha3Bbeta1 surface expression. Neither alpha3 cytoplasmic domain affected recruitment of chimeric alpha5 integrins to fibronectin-induced focal contacts, and either substituted for the alpha5 cytoplasmic domain in alpha5beta1-mediated cell migration. However, the alpha5/alpha3B chimera localized to cell-cell borders in MDCK or CHO cells to a lesser extent than did the alpha5/alpha3A chimera. To determine whether the alpha3 cytoplasmic domains conferred distinct localization to a nonintegrin protein, we transfected cells with interleukin-2 receptor (IL-2R) chimeras containing the alpha3 cytoplasmic domains. The IL-2R/alpha3A chimera was expressed efficiently on the cell surface, while the IL-2R/alpha3B chimera accumulated intracellularly. Our findings suggest that the alpha3B cytoplasmic domain harbors a retention signal that is regulated in an intact integrin and can alter cell surface expression and distribution of alpha3beta1.