Figure 4.

Schematic representation of the role of the primary cilium in Glis signaling. The localization of Glis proteins to the primary cilium suggests that these proteins are part of a primary cilium-associated signaling pathway. A hypothetical upstream signal (e.g., peptide, mechano-, osmo, or chemosensor)(triangle) through plasma membrane-associated receptors (e.g., G-protein coupled receptors) may regulate the primary cilium localization and activity of Glis. Intraflagellar transport (IFT) proteins may direct anterograde and retrograde movement of Glis proteins within the primary cilium. Upon activation, Glis proteins may undergo post-translational modifications or proteolytic processing resulting in modified Glis proteins that function as transcriptional activators (Glis^A) or repressors (Glis^R). After their translocation to the nucleus, Glis proteins regulate the transcription of target genes through interactions with co-activators (CoA) or co-repressors (CoR). Glis-BS, Glis-binding site.