The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN - Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression

The bullous pemphigoid antigen I (eBPAG1) is a constituent of hemidesmosome s (HDs), cell-substrate adhesion complexes in stratified epithelia. Althoug h its COOH terminus interacts with intermediate filaments, its NH2 terminus is important for its recruitment into HDs. To identify proteins that inter act with the NH2 terminus of human eBPAG1, we performed a yeast two-hybrid screen, which uncovered a protein belonging to the LAP/LERP (for LRR and PD Z domain) protein family with 16 NH2-terminal leucine-rich repeats and a CO OH-terminal PDZ domain. The gene for this LAP/LERP protein comprises at lea st 26 exons located on the long arm of chromosome 5. In most human tissues, several transcripts were detected differing in the coding region situated upstream of or within the PDZ domain. One of the encoded variants was found to correspond to the recently described protein ERBIN. In yeast and in vit ro binding experiments, ERBIN was shown to interact not only with eBPAG1 bu t also with the COOH-terminal region of the cytoplasmic domain of the integ rin beta4 subunit, another component of HDs. Antibodies raised against the COOH terminus showed that ERBIN is expressed in keratinocytes. In transfect ed epithelial cells the protein, however, was not localized in HDs but was either diffusely distributed over the cytoplasm or concentrated at the baso lateral plasma membrane. Because ERBIN had been shown previously to interac t with the transmembrane tyrosine kinase receptor Erb-B2, which in turn ass ociates with the integrin beta4 subunit, we suggest that ERBIN provides a l ink between HD assembly and Erb-B2 receptor signaling.