Ciliopathy proteins establish a bipartite signaling compartment in a C. elegans thermosensory neuron

Abstract

How signaling domains form is an important, yet largely unexplored question. Here, we show that ciliary proteins help establish two contiguous, yet distinct cyclic GMP (cGMP) signaling compartments in Caenorhabditis elegans thermosensory AFD neurons. One compartment, a bona fide cilium, is delineated by proteins associated with Bardet-Biedl syndrome (BBS), Meckel syndrome and nephronophthisis at its base, and requires NPHP-2 (known as inversin in mammals) to anchor a cGMP-gated ion channel within the proximal ciliary region. The other, a subcompartment with profuse microvilli and a different lipid environment, is separated from the dendrite by a cellular junction and requires BBS-8 and DAF-25 (known as Ankmy2 in mammals) for correct localization of guanylyl cyclases needed for thermosensation. Consistent with a requirement for a membrane diffusion barrier at the subcompartment base, we reveal the unexpected presence of ciliary transition zone proteins where no canonical transition zone ultrastructure exists. We propose that differential compartmentalization of signal transduction components by ciliary proteins is important for the functions of ciliated sensory neurons.

Age‐dependent changes in response property and morphology of a thermosensory neuron and thermotaxis behavior in Caenorhabditis elegans

“…The AFD ending in young animals consists of a microtubule‐based cilium embedded in a nest of actin‐rich microvilli (Doroquez et al, 2014; Nguyen, Liou, Hall, & Leroux, 2014; Perkins et al, 1986) (Figure 4a). To test whether AFDs in aged animals undergo morphological changes, we used a number of cell‐specific fluorescent transgenes to examine AFD endings as well as dendrites (Figure 4b,c, and Table , Figure ,).…”

“…The three guanylyl cyclases, GCY‐8, GCY‐18, and GCY‐23, fuel cyclic GMP that gates the TAX‐2/TAX‐4 cation channel required for thermosensation (Komatsu et al, 1996,1999). GCY‐8, GCY‐18, and GCY‐23 are localized to the actin‐rich microvilli, whereas TAX‐2 and TAX‐4 subunits are enriched in the cilium (Coburn & Bargmann, 1996; Inada et al, 2006; Komatsu et al, 1996; Nguyen et al, 2014). While missing one of the three guanylyl cyclases has minimal effects on AFD responses to thermal stimuli, elimination of all three abolishes AFD responses (Kuhara, Ohnishi, Shimowada, & Mori, 2011; Ramot, MacInnis, & Goodman, 2008; Takeishi et al, 2016).…”

“…Single‐copy transgenes that express gcy‐8 at near‐physiological level may help to solve this issue. As GCY‐8 is localized to the microvilli (Nguyen et al, 2014), disorganized or shrunken microvilli associated with F‐actin loss may lead to redistribution of GCY‐8 and other molecules important for thermosensory transduction, such as the G protein‐coupled receptor SRTX‐1 and the CNG channel subunits TAX‐2 and TAX‐4 (Colosimo et al, 2004; Nguyen et al, 2014), which potentially change the spatiotemporal patterns of calcium dynamics. An intriguing hypothesis is that patterned AFD calcium dynamics evoked by thermal stimuli specify the valence and magnitude of synaptic signals to AIY that instruct thermotaxis behaviors (Kuhara et al, 2011; Hawk et al, 2018; Nakano et al, 2020).…”

Antagonistic regulation of trafficking to Caenorhabditis elegans sensory cilia by a Retinal Degeneration 3 homolog and retromer

“…We next tested whether rdl-1 was required in a different sensory neuron for enrichment of rGCs in the sensory cilium. GCY-8 is specifically expressed in thermosensory AFD neurons, and is highly enriched in their cilia (17,48). We found that GCY-8, like GCY-9, required rdl-1 to be enriched in sensory cilia (Fig.…”

“…Other mutations affect kinesinand dynein-dependent transport of cargo into and out of the cilium (i.e., intraflagellar transport) (15). Other genes encode proteins that localize to subcompartments of the cilium and define a complex macromolecular structure within the cilium (16)(17)(18).…”