cis- and trans-regulatory mechanisms of CNG channel targeting and localization in C. elegans

Primary cilia are sensory organelles present on the surfaces of many cell types in metazoans. Mislocalization of concentrated ciliary signaling molecules such as cyclic nucleotide-gated (CNG) channels can impair cell function and lead to disease. Despite recent identifications of cis- and trans-acting factors the vast majority of signaling molecules remain unexplored. Further, identified factors do not address protein- and cell-specificity. Here, I demonstrate that CNG channel subunits localize to ciliary subdomains in C. elegans sensory neurons. This suggests heterogeneity of CNG channel composition across the cilium. My work also identifies cis-acting sequences required for ciliary targeting of TAX-4 (CNGA) and TAX-2 (CNGB) subunits in AWB and ASK neurons. I also demonstrate CNG channel intersubunit dependency on ciliary targeting in different neurons. To address trans-acting factors mediating ciliary targeting of CNG channel subunits I utilized a candidate gene approach and identified Inversin, transition zone proteins, intraflagellar motors, and a MYND-domain protein as factors governing ciliary targeting and localization in a cell-specific manner. I also demonstrate that TAX-2 and TAX-4 are relatively immobile within cilia. These results highlight new understanding of CNG channel targeting and localization in C. elegans..