Expression and function of the splice variant of the human cadherin-11 gene in subordination to intact cadherin-11

Cadherin-11, a member of the type II classic cadherin subfamily, differs from type I family molecules such as P-, E-, and N-cadherins, An isoform of the human cadherin-11 gene, termed the variant form, encodes a truncated protein with a different cytoplasmic domain. The resulting protein does not possess any part of the cytoplasmic domain common to other cadherins, In the present study, analysis of the genomic organization of the cadherin-11 gene revealed that an insertion of 179 bp in an intron generates an alternatively spliced form. The mRNA expression of the variant form of cadherin-11 was examined in normal tissues by reverse transcription-polymerase chain reaction and/or Northern blot analyses. The variant form was expressed in the heart, brain, placenta, lung, and bone, but not in the kidney, skeletal muscle, pancreas, and liver. Western blot analyses revealed that the variant form is expressed as an 85 kDa protein, and that an additional secreted form also exists as an 80 kDa protein originated from cleavage of the intact form. Gene transfer of the variant form into L cells demonstrated that it lacked the adhesion properties characteristic of the intact form of cadherin-11 but enhanced the activity of Ca2+-dependent adhesion of the intact form of cadherin-11, The variant was expressed on the surface together with the intact form and stabilized the interaction between the intact form and beta-catenin, These findings suggest that expression of the variant form of human cadherin-11 may regulate the intact cadherin-11-mediated adhesion and alter the morphogenetic processes during mesenchymal cell differentiation including osteoblasts.