The role of Bro1- domain-containing protein Myopic in endosomal trafficking of Wnt/Wingless

•Myopic (Mop) is a positive regulator of Wingless (Wg) signalling.•Mop regulates the subcellular localization of Wg and Wntless (Wls).•Absence of Mop causes an early-to-late endososomal trafficking defect of Wg.•Mop׳s role in Wnt signaling is conserved in vertebrates.

SummaryWingless (Wg) proteins are secreted-lipid-modified glycoproteins involved in tissue patterning and cell-fate specification. Wg secretion is regulated by a specialized mechanism involving a repertoire of proteins including Wntless (Wls). Here, we show that the Bro1-domain-containing protein Myopic (Mop) is indispensable for endosomal trafficking of Wg and Wls. Reductions in Mop leads to trapping of Wg and Wls in the early endosomes. Overexpression of the endosomal sorting protein Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) rescues the trafficking defect caused by the mop loss of function. The vertebrate homolog of Mop, Histidine domain-containing protein tyrosine phosphatase (HDPTP), was also found to have a conserved role in Wnt trafficking. Our study highlights the importance of early endosomal trafficking for Wg secretion, and identifies a novel role for Mop in Wg signaling.