Ciliopathy proteins establish a bipartite signaling compartment in aC. elegansthermosensory 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.

Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C. elegans

“…Ectopic expression of GCY-23(D927A) in AWB failed to elicit temperature-evoked responses (Figure 3B). Importantly, all three AFD-rGCs, as well as GCY-23(D927A) tagged with GFP were enriched at the distal dendritic tips in AWB (Figure 3C), similar to the localization pattern of these rGCs in AFD (Nguyen et al, 2014). We conclude that thermosensitive responses conferred by GCY-23 require its cyclase activity.…”

“…Similar to observations in mammalian photoreceptors, these mechanisms include the high density and compartmentalization of thermosensory molecules in the membranes of the complex AFD microvilli (Nguyen et al, 2014), as well as T c -dependent adaptation of T* AFD that decreases gain and increases thermosensitivity (Biron et al, 2006; Ramot et al, 2008; Yu et al, 2014). The expression of highly thermosensitive AFD-rGCs together with neuron-specific amplification and adaptation mechanisms allows AFD, and hence C. elegans , to be exquisitely temperature sensitive across a wide temperature range.…”

“…The gcy-8, gcy-18 and gcy-23- encoded rGCs are expressed specifically in AFD, and are localized to the specialized AFD sensory endings (Inada et al, 2006; Nguyen et al, 2014). Temperature-evoked currents in AFD are abolished in animals triply mutant for gcy-8, gcy-18 and gcy-23 (Ramot et al, 2008), indicating that these rGCs together are necessary for thermotransduction.…”

Shared and Distinct Mechanisms of Compartmentalized and Cytosolic Ciliogenesis

“…Notably, both the mammalian sperm annulus and the Drosophila sperm compartmentalized cilium contain TZ proteins that appear to provide barrier-like functions outside of canonical Y-links. Such a divergent role for TZ proteins are likely not unique, as it has also been ascribed to a signaling compartment found proximal to the cilium of a C. elegans thermosensory neuron [48]. …”

Receptor Guanylyl Cyclases in Sensory Processing

“…The three rGCs, GCY-8, GCY-18, and GCY-23, are exclusively expressed in AFD (37, 64), and participate in isothermal tracking (59, 65) and migration in linear thermal gradients (66). Recently, it has been shown by ectopic expression in diverse cell types that these rGCs are indeed direct thermosensor molecules, and that both the extracellular and ICDs are necessary for sensation (28).…”