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Subcellular localization

Ciliary associated gene, Nucleoplasm, Cytosol

Functional category

• Motile cilium & axoneme
• Trafficking (BBSome
• small GTPases
• vesicular transport
• ATPases)
• Ciliary assembly/disassembly

Function

Most positive regulators identified in our screens, including Rab34, Pdcl, and Tubd1, were involved in ciliary functions, confirming the central role for primary cilia in Hh signaling. PDCL positively regulates heterotrimeric G-protein signaling by functioning as a chaperone for the assembly of G-protein βγ dimers (Lukov et al., 2005). In many systems, disruption of the Pdcl gene leads to a decline in Gβγ protein levels and failure of G-protein signaling. Phylogenetic analysis of the phosducin-like clade hints at a cilium-associated function for Pdcl, in addition to a role in heterotrimeric G-protein signaling (Figures S3A and S3D). SHH was unable to induce the expression of the direct target genes Gli1 or Ptch1 in Pdcl−/− cells, although it could induce a decrease in GLI3R, consistent with low-level Hh signaling (Figures 4B and S3E). The frequency of primary cilia was modestly reduced in Pdcl−/− cells, without significant change in ciliary length (Figures 4G and S3F). However, there was a severe defect in SHH-induced accumulation of SMO in the ciliary membrane (Figures 4H and 4I). We note that PDCL could also influence Hh signaling by impairing the activity of heterotrimeric G proteins, such as the screen hit Gαi3 (Figure 1B), that antagonize PKA activity (29290584).