Glial septins cell non-autonomously regulate a subset of C. elegans sensory cilia via transition zone independent mechanisms

The sensory and signaling roles of primary cilia rely on compartmentalization mechanisms that establish the organelle's protein and lipid composition. Septins, a family of cytoskeletal GTPases, are proposed to regulate a membrane diffusion barrier, or 'gate', at the ciliary transition zone (TZ) of mammalian cells. Here, we examine septin ciliary functions in vivo, within the sensory organs of Caenorhabditis elegans. Loss of one or both nematode septin genes (unc-59, unc-61) disrupts a small subset of cilia (eg. phasmid cilia), causing short and mispositioned axonemes due to truncated dendritic processes. Interestingly, septins do not appear to function at the ciliary TZ; mutants display normal TZ gating and localisations of the MKS and NPHP module gating complexes. Furthermore, double mutant analyses reveal a lack of septin gene interaction with the MKS & NPHP module pathways. Strikingly, via cell-specific rescue experiments, we find that UNC-61 regulates phasmid neuronal cilia via cell non-autonomous mechanisms, within the glial cells that form the sensory pore. We also find that endogenous UNC-61 localises to phasmid organ-associated cell junctions, and provide evidence that septin gene loss disrupts junction integrity. Together, our data uncovers an unexpected function for glial septins in regulating a subset of sensory neuronal cilia. We propose that this cell-nonautonomous role involves septins functioning at cell junctions.