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Journal: Communications Biology
Article Title: PIP 2 determines length and stability of primary cilia by balancing membrane turnovers
doi: 10.1038/s42003-022-03028-1
Figure Lengend Snippet: a Summary of membrane turnover and regulation of ciliary length. Ciliary length remains stable because membrane insertion and membrane removal are balanced. Top: Cilia grow by fusion of Golgi-derived vesicles with the periciliary membrane. Blocking vesicle fusion by DN Rab8 or brefeldin A blocks growth and reduces ciliary length if membrane removal continues. Elongation of the ciliary membrane is accompanied by elongation of ciliary microtubules (green). Bottom: Endocytosis and ciliary fission reduce ciliary length. Fission can be induced by PIP 2 increase (synthesis or impaired Inpp5e), activation of G-protein coupled receptors (GPCR) or serum exposure. Blocking these processes by PIP 2 depletion, TMSß, DN Rac1, alisertib or tubacin increases ciliary length if vesicle fusion continues. Ciliary microtubules need to be severed for ciliary shortening. b Proposed molecular pathway of ciliary fission. Recruitment of PIPK and deficiency of the 5-phosphatase Inpp5e lead to an increase in ciliary PIP 2 . Serum addition and agonist binding (in the presence of DN dynamin) have the same effect. The PIP 2 increase can be prevented by sequestering PIP 2 using PH(PLCδ1) or by constitutive expression of the 5-phosphatase Inp54p. The PIP 2 increase leads to polymerisation of g-actin to f-actin, presumably amplified by help of the Rho kinases Rac1 and Cdc42. Actin polymerisation can be prevented by TMSß and latruculin A. AurkA and HDAC6 likely act downstream of actin polymerisation and could work by microtubule depolymerisation, which is also required for ciliary fission. AurkA and HDAC are inhibited by alisertib, respectively, tubacin.
Article Snippet:
Techniques: Membrane, Derivative Assay, Blocking Assay, Activation Assay, Binding Assay, Expressing, Amplification