Regulation of Naked2 by transforming growth factor-alpha and Wnt signaling

Abstract

Naked family members (Drosophila Naked Cuticle and mammalian Naked1 and Naked2) have been identified as inducible antagonists of canonical Wnt signaling. We previously reported that Naked2, but not Naked1, interacts with the cytoplasmic tail of transforming growth factor ƒÑ (TGFƒÑƒw, thereby coating TGFƒÑ-containing exocytic vesicles and directing these vesicles to the basolateral corner of polarized epithelial cells. We have designated Naked2 a cargo recognition and targeting (CaRT) protein required for TGFƒÑ basolateral cell surface delivery. Despite the importance of its role in both Wnt signaling and TGFƒÑ trafficking, the regulation of Naked2 has not been characterized. Moreover, in vivo roles for Naked2 in these biological processes are largely unknown. To address these deficiencies, I have examined the regulation of Naked2 expression in the context of canonical Wnt signaling and epidermal growth factor receptor (EGFR) signaling, and I have generated a targeted conditional disruption of Naked2 in the mouse.