The CEACAM1-L glycoprotein associates with the actin cytoskeleton and localizes to cell-cell contact through activation of rho-like GTPases

Associations between plasma membrane-linked proteins and the actin cytoskel eton play a crucial role in defining cell shape and determination, ensuring cell motility and facilitating cell-cell or cell-substratum adhesion. Here , we present evidence that CEACAM1-L, a cell adhesion molecule of the carci noembryonic antigen family, is associated with the actin cytoskeleton. We h ave delineated the regions involved in actin cytoskeleton association to th e distal end of the CEACAM1-L long cytoplasmic domain. We have demonstrated that CEACAM1-S, an isoform of CEACAM1 with a truncated cytoplasmic domain, does not interact with the actin cytoskeleton. In addition, a major differ ence in subcellular localization of the two CEACAM1 isoforms was observed. Furthermore, we have established that the localization of CEACAM1-L at cell -cell boundaries is regulated by the Rho family of GTPases. The retention o f the protein at the sites of intercellular contacts critically depends on hemophilic CEACAM1-CEACAM1 interactions and association with the actin cyto skeleton. Our results provide new evidence on how the Rho family of GTPases can control cell adhesion: by directing an adhesion molecule to its proper cellular destination. In addition, these results provide an insight into t he mechanisms of why CEACAM1-L, but not CEACAM1-S, functions as a tumor cel l growth inhibitor.