PIP2 determines length and stability of primary cilia by balancing membrane turnovers

• Published in: Communications biology 2022-01, Vol.5 (1), p.93-93, Article 93
• Main Authors: Stilling, Simon, Kalliakoudas, Theodoros, Benninghoven-Frey, Hannah, Inoue, Takanari, Falkenburger, Björn H
• Format: Article
• Language: English
• Subjects: 14/10; 14/35; 631/80/86/2365; 692/4017; Actin; Aurora kinase; Biology; Biomedical and Life Sciences; Cell cycle; Cilia; Dimerization; Dynamin; Histone deacetylase; Life Sciences; Organelles; Phosphatidylinositol; Phosphatidylinositol 4,5-diphosphate; Phospholipid composition; Phospholipids; Rho-associated kinase
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03028-1

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. By using methods to synthesise or degrade PIP 2 selectively in the ciliary membrane, Stilling et al. find that PIP 2 levels determine the length of primary cilia. They show that various pathways converge on PIP 2 which induces ciliary fission in a manner dependent on actin, AurkA and HDAC6.