PIP 2 determines length and stability of primary cilia by balancing membrane turnovers.

Primary cilia are sensory organelles on many postmitotic cells. The ciliary membrane is continuous with the plasma membrane but differs in its phospholipid composition with phosphatidylinositol 4,5-bisposphate (PIP 2 ) being much reduced toward the ciliary tip. In order to determine the functional significance of this difference, we used chemically induced protein dimerization to rapidly synthesize or degrade PIP 2 selectively in the ciliary membrane. We observed ciliary fission when PIP 2 was synthesized and a growing ciliary length when PIP 2 was degraded. Ciliary fission required local actin polymerisation in the cilium, the Rho kinase Rac, aurora kinase A (AurkA) and histone deacetylase 6 (HDAC6). This pathway was previously described for ciliary disassembly before cell cycle re-entry. Activating ciliary receptors in the presence of dominant negative dynamin also increased ciliary PIP 2 , and the associated vesicle budding required ciliary PIP 2 . Finally, ciliary shortening resulting from constitutively increased ciliary PIP 2 was mediated by the same actin - AurkA - HDAC6 pathway. Taken together, changes in ciliary PIP 2 are a unifying point for ciliary membrane stability and turnover. Different stimuli increase ciliary PIP 2 to secrete vesicles and reduce ciliary length by a common pathway. The paucity of PIP 2 in the distal cilium therefore ensures ciliary stability.