Wingless (Wg) signals mostly from the endosome not from the plasma membrane, according to Seto and Bellen (page 95).

The Wnt/Wg pathway controls numerous steps in development and is tightly regulated. The receptor and coreceptor for Wg sit on the cell surface where they can bind extracellular ligand, but signaling relies on the presence of downstream proteins.

One possible site for uniting receptors and signaling proteins is on endosomes—after endocytosis of the Wg–receptor complex, but before lysosomal degradation. To test this possibility, Seto and Bellen asked what happened to Wg signaling when they used mutations in key genes to block individual vesicle trafficking steps between the cell surface and the lysosome.

When endocytosis was inhibited, a large excess of Wg accumulated on the cell surface but little downstream signaling occurred. Similarly, when endocytosis was allowed, but vesicle fusion to the endosome was hindered, little signaling occurred. By contrast, when the Wg–receptor complex made it to the endosome but was barred from moving into multivesicular bodies and lysosomes, signaling was robust and persistent. Overexpression of Hrs, a protein that promotes multivesicular body formation, decreased Wg signaling.

Endosome-based signaling may provide precise temporal regulation because the cell can control the duration a protein complex stays in the endosome. That regulatory control may be important in the Wg pathway, as some effector proteins are known to need more or less ligand for activation.