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Abstract
Primary cilia function as critical signaling hubs whose absence leads to severe disorders collectively known as ciliopathies, yet our knowledge of ciliogenesis remains limited. Here I show that Smo induces ciliogenesis through two distinct yet essential non-canonical Hh pathways in several cell types including primary neurons. Surprisingly, Sonic Hh ligand (Shh) activation of Smo can induce autophagy via an LKB1-AMPK axis to remove the satellite pool of OFD1. This is required, but not sufficient, to induce ciliogenesis. Additionally, Smo activates the Gαi-LGN-NuMA-Dynein axis, which results in accumulation of a portion of OFD1 at centrioles at early stages of ciliogenesis. Both pathways are critical for redistribution of BBS4 from satellites to centrioles, and this also relies on centriolar translocation of OFD1. Notably, different Smo agonists, which activate Smo distinctly, activate one or the other of these pathways and only recapitulate the activity of Shh in combination. These studies provide new insights into physiological stimuli (Hh) that activate autophagy and promote ciliogenesis and introduce a novel role for the Gαi-LGN-NuMA-Dynein complex in this process.
