A short isoform of carcinoembryonic-antigen-related rat liver cell-cell adhesion molecule (C-CAM/gp110) mediates intercellular adhesion. Sequencing and recombinant functional analysis.

Rat liver cell-cell adhesion molecule (C-CAM) is a type I transmembrane glycoprotein belonging to the immunoglobulin (Ig)-superfamily. Within this family it is related to the carcinoembryonic antigen (CEA) proteins. C-CAM, previously known as gp110, cell-CAM 105, HA4/pp120 or ecto-ATPase, is a highly glycosylated protein with an apparent M(r) or 100,000-115,000 and an isoelectric point of 3-3.5. It was analysed as a molecule that stimulates reaggregation of isolated hepatocytes. So far three different isoforms have been cloned. Only the isoform with a long intracellular tail (71 amino acids), C-CAM1, was shown to be involved in intercellular adhesion. C-CAM2, an isoform with only 10 cytoplasmic amino acids and a slightly different N-terminal Ig-like loop did not function as an adhesion molecule. In this study we show the existence of another short C-CAM isoform (C-CAM2a), which is an alternatively spliced product of the C-CAM1 gene. Like C-CAM2, it has a short cytoplasmic tail, but in the extracellular region it is identical to C-CAM1. To investigate whether C-CAM2a can function as an adhesion molecule, we stably expressed the corresponding cDNA in Chinese hamster ovary (CHO) cells. In these cells, we detected a specific increase of intercellular adhesion, indicating that, in contrast to the other short isoform, C-CAM2a can induce adhesion. This adhesion is homophilic and Ca2+ independent.