The DHHC palmitoyltransferase approximated regulates fat signaling and Dachs localization and activity

Signaling via the large protocadherin Fat (Ft), regulated in part by its binding partner Dachsous (Ds) and the Golgi-resident kinase Four-jointed (Fj), is required for a variety of developmental functions in Drosophila. Ft and, to a lesser extent, Ds suppress overgrowth of the imaginal discs from which appendages develop and regulate the Hippo pathway [1-5] (reviewed in [6]). Ft, Ds, and Fj are also required for normal planar cell polarity (PCP) in the wing, abdomen, and eye and for the normal patterning of appendages, including the spacing of crossveins in the wing and the segmentation of the leg tarsus (reviewed in [7-9]). Ft signaling was recently shown to be negatively regulated by the atypical myosin Dachs [10, 11]. We identify here an additional negative regulator of Ft signaling in growth control, PCP, and appendage patterning, the Approximated (App) protein. We show that App encodes a member of the DHHC family, responsible for the palmitoylation of selected cytoplasmic proteins, and provide evidence that App acts by controlling the normal subcellular localization and activity of Dachs.