Based on original genetic evidence in Drosophila and C.elegans, the secretion of Wnt proteins needs the function of a dedicated protein Wntless (Wls) also known under various different other names (Evi/Sprinter/Mig-14/Gpr177; see table below). The Wls protein is a multiple-pass transmembrane molecule. Because of the lack of Wnt secretion in Wls mutant cells, it is thought that Wls is a transporter molecule that is specific for Wnt proteins. Nygaard  et al (2020) reported on a 3.2 Å resolution cryo-EM structure of WNT8A bound to  Wntless, with a  Wnt hairpin inserted into a conserved hydrophobic cavity in the Wntless protein. The gene is highly conserved and has been found in organisms ranging from mice to Planaria.

See the page on Wnt secretion. 

Review by  Routledge D, Scholpp, S. Mechanisms of intercellular Wnt transport. Development. 2019 May 15;146(10). pii: dev176073. doi: 10.1242/dev.176073.




C. elegans mig-14 loss Wnt signaling (Yang, 2008)
Drosophila Wntless/Evi/Sprinter segment polarity (Banziger, 2006; Bartscherer, 2006; Goodman, 2006).
Mouse Gpr177 early axis defect (Fu 2009)
Planaria Smed-Evi/Wntless regeneration defects (Adell, 2009)