MKS-NPHP module proteins regulate ciliary shedding in Paramecium
Ciliogenesis is a general process in eukaryotic cells and its different steps begin to be well characterised. However, the molecular mechanisms leading to decilation or ciliary shedding are still poorly understood. This process, observed from unicellular organisms such as Chlamydomonas or Paramecium to multiciliated cells from trachea or fallopian tube of vertebrates, seems to be a general process since recent observations demonstrates its requirement during the cell cycle or neurogenesis. Interestingly, in all cellular models, ciliary shedding occurs distal to the transition zone, essentially known to act as a diffusion barrier between the intracellular space and the cilium, suggesting conserved molecular mechanisms.\n\nTo determine if MKS and NPHP modules, known to cooperate to establish transition zone formation and function, could control ciliary shedding, we studied in Paramecium the function of TMEM216/MKS2 and TMEM107 (two members of the MKS module), NPHP4 (one member of the NPHP module), CEP290/NPHP6 and RPGRIP1L/MKS5. We show that all these proteins are recruited to the TZ as soon as growing cilia are detected and localise with a 9-fold symmetry at the level of the axonemal plate. Interestingly, we demonstrate that the depletion of the two MKS module proteins induces spontaneous cilia shedding, while the depletion of either NPHP4, CEP290 or RPGRIP1L inhibits the process. Our results constitute the first evidence for a role of conserved TZ proteins in deciliation and open new directions for understanding motile cilia physiology.