LIVER-INTESTINE CADHERIN - MOLECULAR-CLONING AND CHARACTERIZATION OF A NOVEL CA2-DEPENDENT CELL-ADHESION MOLECULE EXPRESSED IN LIVER AND INTESTINE()

A novel member of the cadherin family of cell adhesion molecules has b een characterized by cloning from rat liver, sequencing of the corresp onding cDNA, and functional analysis after heterologous expression in nonadhesive S2 cells. cDNA clones were isolated using a polyclonal ant ibody inhibiting Ca2+-dependent intercellular adhesion of hepatoma cel ls. As inferred from the deduced amino acid sequence, the novel molecu le has homologies with E-, P-, and N-cadherins, but differs from these classical cadherins in four characteristics. Its extracellular domain is composed of five homologous repeated domains instead of four chara cteristic for the classical cadherins. Four of the five domains are ch aracterized by the sequence motifs DXNDN and DXD or modifications ther eof representing putative Ca2+-binding sites of classical cadherins. I n its NH2-terminal region, this cadherin lacks both the precursor segm ent and the endogenous protease cleavage site RXKR found in classical cadherins. In the extracellular EC1 domain, the novel cadherin contain s an AAL sequence in place of the HAV sequence motif representing the common cell adhesion recognition sequence of E-, P-, and N-cadherin. I n contrast to the conserved cytoplasmic domain of classical cadherins with a length of 150-160 amino acid residues, that of the novel cadher in has only 18 amino acids. Examination of transfected S2 cells showed that despite these structural differences, this cadherin mediates int ercellular adhesion in a Ca2+-dependent manner. The novel cadherin is solely expressed in liver and intestine and was, hence, assigned the n ame LI-cadherin. In these tissues, LI-cadherin is localized to the bas olateral domain of hepatocytes and enterocytes. These results suggest that LI-cadherin represents a new cadherin subtype and may have a role in the morphological organization of liver and intestine.