Both LKB1-AMPK and Gαi-LGN-NuMA-dynein axes are required for BBS4 recruitment to basal body. (A) SIM images indicating BBS4 localization with respect to γ Tubulin as a centriole marker in RPE1 WT, Smo KO, and cells depleted of OFD1(1+2+3), LKB1, AMPK, Gαi (1+2+3), LGN, and NuMA and treated with Ciliobrevin A (100 nM) at LCD, with or without Shh for 5 h. Yellow and white arrows point to the presence or absence, respectively, of BBS4 at centrioles. (B) Quantification of BBS4 total cell intensity and BBS4 centriole intensity at different conditions as indicated. The quantifications were done using images taken with confocal microscopy. (C) Graphical abstract indicating how noncanonical Hh induces ciliogenesis via Smo activity. (i and ii) Smo activates LKB1 to promote the activation of autophagy to remove the satellite pool of OFD1 (i) and release BBS4 from satellites (ii). It also activates the Gαi-LGN/NuMA/dynein axis to promote the translocation of a portion of OFD1 to the centrioles and recruitment of BBS4 to basal body and cilia.