Filamentous actin binding ability of cortactin isoforms is responsible for their cell–cell junctional localization in epithelial cells

Cortactin is an F-actin binding protein that contributes to cytoskeleton remodelling. We identified five isoforms of mouse cortactin that differ in the number of tandem 37-amino acid repeats, named cortactin repeats. The transcription of minor isoforms with 4.5, 3.5 or 2.5 cortactin repeats was low in most adult tissues whereas an isoform with 4.5 cortactin repeats was highly transcribed in the adult brain. In accordance with the brain-specific upregulation of a minor isoform, a brain-specific novel 72-kDa cortactin protein was identified. Major isoforms with 6.5 or 5.5 cortactin repeats bound F-actin more robustly than minor isoforms in vitro. All isoforms were concentrated at cell–cell junction sites in epithelial cells. Deletion mutants lacking whole cortactin repeats did not bind F-actin and were not concentrated at cell–cell junction sites. Thus, the F-actin binding ability is mostly correlated with the number of cortactin repeats and is required for the cell–cell junctional localization.