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Fig. 9. Model of endocytosis and Hh signaling. In the absence of Hh Ptc, Smo and the cytoplasmic components are endocytosed. All the components including some of the Ptc, are degraded; Ci is proteolyzed to its repressor form (Ci75). Most of the Ptc recycles to the plasma membrane (broken arrow) permitting Ptc to repeat the cycle and regulate Smo levels in a `catalytic' manner. In the presence of Hh the initial events are similar. Ptc bound to Hh is now sorted for degradation while Smo splits apart, is activated and full-length Ci (Ci155) is generated. Membrane and microtubule association of Cos2 and Fu decreases upon Hh signaling (Stegman et al., 2004) favoring their early release from Smo and vesicles. Activated Smo recycles to the plasma membrane where it activates more Ci; Cos2 and Fu are destabilized (Lum et al., 2003; Ruel et al., 2003), suggesting that once Ci is activated, Cos2 and Fu are degraded. Shi, Rab5 and Rab7 denote where these components function within the endocytic cycle.

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