Skip to main content
Fig. 4 | BMC Biology

Fig. 4

From: Lipid metabolism fattens up hedgehog signaling

Fig. 4

The regulation of smoothened trafficking by cholesterol. a The levels of transmembrane receptors such as smoothened (SMO) at the plasma membrane are determined by the balance between the rates of supply by exocytosis and internalization by endocytosis. Following endocytosis, receptors are either recycled back to the membrane or degraded [29]. In the absence of sonic hedgehog (SHH), patched1 (PTCH1) reduces the concentration of cholesterol in the membranes of endosomal vesicles, biasing plasma membrane SMO toward internalization and degradation [101, 139]. b SHH binding redistributes PTCH1 from the primary cilium and SMO-containing endosomal vesicles [93, 141]. In the absence of PTCH1, the concentration of cholesterol within endosomal membranes is elevated [139]. Elevated cholesterol levels within endosomal membranes allow SMO to accumulate in the plasma membrane by reducing its rate of internalization and degradation [101, 139]. Whether PTCH1 activity also modulates cholesterol levels in the membranes around the base or within the shaft of the primary cilium remains to be determined. c In Smith-Lemli-Opitz syndrome (SLOS), the associated reduced cellular cholesterol levels decrease the accumulation of SMO in the cilium in response to SHH [118]. This may be due to a requirement for direct molecular interaction between cholesterol and SMO for SMO cilia entry. Alternatively, reduced cholesterol levels may indirectly decrease SMO levels in the cilium by disrupting the kinetics of endocytic, recycling, or exocytic vesicle trafficking to and from the plasma membrane

Back to article page