Role of membrane protein shrew-1/AJAP1 in epithelial plasticity in vitro and in vivo

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The fine tuning of adhesion dynamics is a central feature of morphological epithelial plasticity impor-tant in physiological (e.g. embryogenesis) as well as in pathophysiological processes (e.g. carcinoma development). Our findings that membrane protein shrew-1/AJAP1 acts as a novel modulator of adhe-sion protein E-cadherin internalization induced by EGF-mediated activation of receptor tyrosine kinase Her2 are highly relevant for these issues. This is also true for the newly discovered interplay between shrew-1/AJAP1 and ezrin, a member of the ERM protein family. ERMs link membrane proteins with the cytoskeleton and contribute to the organization of signalling platforms for membrane receptors (e.g. EGF receptor family) thereby influencing growth and differentiation. Deciphering mechanism(s) controlling the interplay between shrew-1/AJAP1 and ezrin as well as further analysis of shrew-1/AJAP1’s gene function using mammary gland development as a model system in vitro and in vivo are central aims of this proposal. Furthermore, our structure function analyses of shrew-1/AJAP1 pro-tein revealed different signal peptides, two of which lead the same protein. The third signal peptide guides a truncated version of shrew-1/AJAP1 composed of its cytoplasmic domain. In this context we aim to investigate a) the differential use of shrew-1/AJAP1’s signal peptides and b) the function of the short shrew-1/AJAP1 isoform.