Key signaling pathways in development depend on the dynamic cellular compartment created by the primary cilium. In vertebrates, the Shh pathway is activated only when the plasma membrane-localized Shh effector Smo accumulates in the primary cilium, where Smo regulates cilium-localized transcription factors and tissue development. In the unicellular biflagellated green alga Chlamydomonas, the adhesion receptor SAG1 is present on the plasma membrane and restricted from entering the cilium by a functional barrier. Upon cilium-generated signaling during cell-cell interactions, however, SAG1 moves to the bases of the cilia, overcomes the barrier, and moves onto the ciliary membrane. A crucial unanswered question in biology is how cells establish and regulate the protein composition of cilia during activation of signaling pathways. Unlike in animal cells, we can isolate cilia from Chlamydomonas and we can inactivate the ciliary transport machinery, IFT. Here, we will exploit the multiple advantages of this simple system to study the cellular and molecular mechanisms that underlie the ability of cells to regulate the ciliary localization of a membrane protein during cilium-generated signaling.
Cilia/flagellar are key sensory organelles essential for development and homeostasis, and disruption of ciliary functions underlie important human diseases, the ciliopathies, and cancer. We know little about the unique properties of this organelle that have led to its broad use in signal transduction. Therefore, dissecting the mechanisms that cells use to control the proteins in the cilium that receive sensory information and transmit it to the rest of the cell is critical for understanding development and preventing and treating disease.
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