Cilium-Generated Signaling

Although almost every cell possesses a primary cilium, we know little about the mechanisms that cells use to regulate the protein compositions of the ciliary membrane. During ciliogenesis, ciliary membrane proteins, along with structural and signaling proteins, are carried through a complex ciliary diffusion barrier at the base of the organelle by intraflagellar transport (IFT). Disruption of the barrier leads to several human diseases of cilia, the ciliopathies. A favored model is that signaling-triggered accumulation of previosuly excluded membrane proteins in fully formed cilia also requires IFT, but direct evidence is lacking. We recently developed a new system to study entry of a membrance protein into the cilia of Chlamydomonas during ciliary signaling. In resting cells, a ciliary signaling component, the integral membrane polypeptide SAG1, is uniformly distributed over the plasma membrane and excluded from the ciliary membrane. We identified a cellular pathway in Chlamydomonas for regulated polarization of a pre-existing ciliary adhesion and signaling receptor from the plasma membrane to the peri-ciliary membrane. The protein undergoes rapid, regulated internalization from the plasma membrane, associates with underlying cytoplasmic microtubules, becomes enriched along those microtubules at their sites of origin at the basal bodies, and reappears on the cell surface in the peri-ciliary membrane. Ciliary adhesion-induced signaling triggers rapid redistribution of the protein to the apical ends of the cells concomitantly with entry into the cilia.

SAG1-HA distribution on resting gametes
SAG!-HA distribution on activated gametes