Balancing the length of the distal tip by septins is key for stability and signalling function of primary cilia

Abstract

Primary cilia are antenna-like organelles required for signalling transduction. How cilia structure is mechanistically maintained at steady-state to promote signalling is largely unknown. Here, we define that mammalian primary cilia are formed by middle and distal segments, in analogy to sensory cilia of lower eukaryotes. The analysis of middle/distal segmentation indicated that perturbations leading to cilia over-elongation influenced middle or distal segment length with a different impact on cilia behaviour. We identified Septins as novel repressors of distal segment growth. We show that Septins control the localisation of MKS3 and CEP290 required for a functional transition zone, and through this the entrance of the microtubule-capping kinesin KIF7, a cilia-growth inhibitor, into the cilium. Live-cell imaging and analysis of sonic-hedgehog (SHH) signalling activation established that distal segment over-extension increased cilia excision events and decreased SHH activation. Our data underlies the importance of understanding cilia segmentation for length control and cilia-dependent signalling. ### Competing Interest Statement The authors have declared no competing interest.