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Figure 1


Fig. 1. Wnt biogenesis and interaction with receptors. (A) Wnt biogenesis for short- and long-range signaling. Wnt palmitoylation occurs within the endoplasmic reticulum (ER) and requires Porcupine (Porc). Wntless (Wls) probably acts in the Golgi apparatus and exocytic vesicles (EV), and is required for Wnt to reach the cell surface for secretion (Banziger et al., 2006; Bartscherer et al., 2006). VPS-35 and the retromer complex appears to be required only for Wnt (EGL-20) destined for long-range signaling (Coudreuse et al., 2006; Prasad and Clark, 2006). (B) In the absence of Wnt, ß-catenin is unstable. (C) The association of Wnt with the Fz-Lrp5/6 co-receptor complex stabilizes ß-catenin, via the sequential phosphorylation (P) of the Lrp5/6 cytoplasmic domain, likely by Gsk3 and Ck1{gamma} (Davidson et al., 2005; Zeng et al., 2005), to activate the canonical pathway. Lrp5/6 phosphorylation recruits the scaffolding protein Axin (Mao et al., 2001; Tamai et al., 2004). Dishevelled (Dvl) may act via the recruitment or inhibition of the Axin complex. Wnt5a can bind Ror2, and antagonize Tcf/ß-catenin transcription downstream of ß-catenin stabilization (Mikels and Nusse, 2006).