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. 2021 Jun 23;220(9):e202010177. doi: 10.1083/jcb.202010177

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© 2021 Lv et al.

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Figure 8. — Model for regulating ciliary Smo levels.(A) Ptch1-bound Wwp1 and the short isoform of Ube2l3 localize to cilia at the basal state and ubiquitinate any Smo that enters the cilium. Ubiquitinated Smo is the cargo for IFT, causing it to be removed from the cilium. Upon pathway activation, Ptch1 with associated Wwp1 exits the cilia, allowing Smo to accumulate in the cilia and activate the downstream steps of the pathway. Hh, Hedgehog. (B) Smo has K63-linked Ub chains at lysine 444 and lysine 448 in intracellular loop 3. The ubiquitinated Smo is recognized by the BBSome, which couples to IFT-B through Lztfl1/IFT25/IFT27 and removed out of cilia by the retrograde IFT.