AnnexinA2 regulates beta 1 integrin internalization and intestinal epithelial cell migration

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The gastrointestinal epithelium functions as an important barrier that separates luminal contents from underlying tissue compartment and is vital in maintaining mucosal homeostasis. Inflammatory disorders induce epithelial injury and mucosal wounds that compromise the critical epithelial barrier. In response to injury, intestinal epithelial cells (IECs) rapidly migrate to reseal wounds. We have previously observed that a membrane associated and actin binding protein, Annexin 2 (AnxA2) is up‐regulated in migrating IECs and promotes wound closure. To address the mechanisms by which AnxA2 promotes cell migration, we generated IEC lines with stable down regulation of AnxA2 using shRNA. Loss of AnxA2 increased IEC cell‐matrix adhesion that was associated with increased β1 integrin protein expression with no change to mRNA levels. Since cell migration requires dynamic turnover of integrin based adhesions, we determined if AnxA2 influences β1 integrin internalization from the cell surface thereby regulating IEC migration. Indeed, pulse‐chase biotinylation assays identify a 6 fold increase in β1 integrin at the cell surface and significantly decreased integrin internalization and degradation in IECs lacking AnxA2. These findings support an important role of AnxA2 in controlling dynamics of β1 integrin, cell –matrix adhesion turnover, cell migration and, therefore, wound closure.