Figure 9

Model for regulation of axonemal tubulin acetylation in the primary cilium by PP1 and I-2. Axonemal tubulin acetylation is regulated by the balance of acetyltransferase (HAT) and deacetylases (HDACs). The tubulin-localized HDAC binds and interacts with MT-associated PP1. The activity of HDAC is negatively regulated by phosphorylation, so PP1 dephosphorylation produces activation. The presence of I-2 inhibits this PP1 holoenzyme and keeps the PP1-bound HDAC inactive. As a result the axonemal tubulin is highly acetylated and stabilized during formation of the primary cilium. When I-2 is depleted or dissociated from PP1-HDAC complex, PP1 dephosphorylates and activates HDAC, and results in ciliary tubulin deacetylation and destabilization of the axoneme of the primary cilium. Inhibition of PP1 by calyculin A or inhibition of HDAC by TSA can compensate for the function of I-2 in this pathway to increase tubulin acetylation.