FIGURE 1.

Model of ectocytosis from the mammal primary cilium. (A) The intraflagellar transport system (IFT) participates in the assembly and maintenance of the primary cilium through the transport of molecular cargos by IFT-A and IFT-B protein complexes. In quiescent cells, the primary ciliary membrane is enriched in PI(4)P due to the presence of the ciliary phosphatase INPP5E which converts PI(4,5)P2 to PI(4)P. (B) Following a proliferation growth signal (1), the ciliary phosphatase INPP5E is removed from the membrane, promoting the redistribution of the phosphoinositide PI(4,5)P₂ in the primary cilium. These membrane changes allow the local polymerization of F-actin through the recruitment of actin-associated proteins, followed by the ectocytosis of ciliary EVs enriched in bioactive molecules. Although ectocytosis following actin polymerization was identified at the cilium tip, F-actin was also observed in the vicinity of ciliary EVs present along the axoneme membrane. The activated Neuropeptide Y receptor type 2 (NPY2R) uses ectocytosis as a constitutive way to exit the cilium (2). The mechanical force (3) generated by the surrounding fluid flow also promotes the release of ciliary EVs.