Fig. 7
Proposed model of cholesterol function in ciliogenesis. Cholesterol in the trans-Golgi network is required for the synthesis of Pi(4)P, which in turn is phosphorylated to Pi(4,5)P2. Pi(4,5)P2 is an integral component of the transition zone of the cilium and hence controls the import and potentially also the export of cargo to and from cilia. This facilitates ciliary signalling such as Hedgehog signalling, which in turn is required for proper development of the heart and anterior structures such as the head and the ear. The Hedgehog cascade is further propagated by cholesterol modifications of Hedgehog (Hh, bound to Patched, Ptc) and of its signal transducer Smoothened (Smo). In the absence of cholesterol, Pi(4,5)P2 accumulation at the cilium is inhibited resulting in impaired cilium formation. In addition, ciliary signalling, for instance Hedgehog signalling, is defective giving rise to ciliopathy phenotypes, which overlap with some of the clinical manifestations of SLOS (i.e., CHD and kidney defects)
