International Worm Meeting,
Cilia are microtubule-based and membrane-bound organelles that serve diverse functions in various organisms and tissues. The ciliary membrane is a tightly regulated region that is enriched with many proteins not found throughout the rest of the cell membrane. Likewise, many proteins found in the cell membrane are excluded from the cilium. The mechanisms by which the cell membrane and ciliary membrane are differentially regulated are unknown. It is proposed that proteins at the base of the cilium participate in cell/ciliary membrane protein sorting, but their molecular identity has not been uncovered. Here, we demonstrate that the B9 domain proteins, TZA-1(Y38F2AL.2) and TZA-2(K03E6.4), function in such a capacity. MKS-3(F35D2.4), a transmembrane protein implicated in the human developmental disorder Meckel-Gruber Syndrome (MKS), normally localizes specifically to the ciliary base in C. elegans. In the absence of TZA-1 or TZA-2, MKS-3 freely enters the cilium, suggesting a requirement of these proteins in restricting ciliary access. Additionally, the transmembrane protein TRAM-1a (C24F3.1a), which normally concentrates directly adjacent to the ciliary base at the dendritic tip, is allowed ciliary access in the absence of TZA-1 or TZA-2. These data provide important insight into a mechanism by which ciliary membrane composition is regulated.