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Subcellular localization

Ciliary associated gene

Functional category

• Small GTPases
• Metabolism
• Signaling (Hedgehog
• GPCRs
• ion channels)
• Ciliary assembly/disassembly

Function

From a genome-wide CRISPR activation (CRISPRa) screen for negative regulators of ciliary function, we find here that the F2R G protein-coupled receptor, sterile alpha and TIR motif-containing 1 (SARM1) hydrolase, ryanodine receptors, peri-centrosomal calcium signaling, and RhoA form a functional pathway that is necessary and sufficient for cilia disassembly. Proteolytic cleavage of F2R by thrombin or other proteases exposes an N-terminal self-activation domain that triggers signaling through Gαq/11, Gα12/13, and Gαi/o (Fig. 2A) (21). To understand how F2r CRISPRa impairs ciliary signaling, we made NIH-3T3 cell lines expressing two F2r-targeting sgRNAs from the screen (sgF2r.A and sgF2r.B), which both increased F2r expression and inhibited Hh signaling (Fig. 1F and fig. S2, A and B)(41160700).