Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis

The tumor suppressor adenomatous polyposis coli (APC) negatively regulates Wingless (Wg)/Wnt signal transduction by helping target the Wnt effector be ta-catenin or its Drosophila homologue Armadillo (Arm) for destruction. In cultured mammalian cells, APC localizes to the cell cortex near the ends of microtubules, Drosophila APC (dAPC) negatively regulates Arm signaling, bu t only in a limited set of tissues, We describe a second fly APC, dAPC2, wh ich binds Arm and is expressed in a broad spectrum of tissues. dAPC2's subc ellular localization revealed colocalization with actin in many but not all cellular contexts, and also suggested a possible interaction with astral m icrotubules, For example, dAPC2 has a striking asymmetric distribution in n euroblasts, and dAPC2 colocalizes with assembling actin filaments at the ba se of developing larval denticles, We identified a dAPC2 mutation, revealin g that dAPC2 is a negative regulator of Wg signaling in the embryonic epide rmis. This allele acts genetically downstream of wg, and upstream of arm, d TCF, and, surprisingly, dishevelled. We discuss the implications of our res ults for Wg signaling, and suggest a role for dAPC2 as a mediator of Wg eff ects on the cytoskeleton, We also speculate on more general roles that APCs may play in cytoskeletal dynamics.