hepaCAM, a novel immunoglobulin‐like cell adhesion molecule, is associated with the actin cytoskeleton and the lipid rafts and is involved in cell‐matrix interaction

We have recently identified a novel gene hepaCAM which encodes a cell adhesion molecule of the immunoglobulin superfamily. Biochemical analyses reveal that hepaCAM is an N‐linked glycoprotein phosphorylated in the cytoplasmic domain, and forms homodimers through cis‐interaction on cell surface. Immunocytochemistry shows that the wild‐type hepaCAM colocalizes with filamentous actin (F‐actin) on the plasma membrane while depolymerization of F‐actin leads to an increased solubilization and a disruption of the subcellular distribution of hepaCAM. Sucrose density gradients demonstrate that hepaCAM partitions into the lipid rafts while dispersion of cholesterol in the lipid rafts alters the buoyancy of hepaCAM. In addition, hepaCAM colocalizes with the lipid raft markers, caveolin‐1 and fyn. Functionally, hepaCAM increases cell spreading on matrices fibronectin and matrigel, delays cell detachment, and enhances wound healing. Furthermore, when the cytoplasmic domain is deleted, hepaCAM mutants do not affect cell surface localization and dimer formation; however, these mutants are less significantly involved in cell‐matrix adhesion and cell motility. Overall, these data indicate that hepaCAM interacts with the actin cytoskeleton and resides in the lipid rafts, and that the cytoplasmic domain of hepaCAM is essential to its function on cell‐matrix interaction and cell motility.