This review highlights the role of ciliary guanylyl cyclases in ciliopathies, suggesting their importance in signal transduction and ciliary function.
Most eukaryotic cells employ a specialized sensory organelle─the cilium─that protrudes from the cell surface as a chemo-mechanical antenna. The dysfunction of cilia is associated with a wide range of human diseases collectively termed ciliopathies. Mounting evidence indicates that nonmotile (primary) cilia orchestrate key developmental and homeostatic processes through spatial regulation of multiple signaling pathways, including Hedgehog, Wnt, and PDGF cascades. Intriguingly, an ancient signal transduction system, guanylyl cyclases (GCs)-cyclic GMP (cGMP) module, is almost exclusively found in ciliated organisms, suggesting coevolution of ciliary architecture and cGMP-mediated signal processing. Although most GCs operate in ciliated cells, the specific membrane GCs which are localized in the cilium and their ciliary functions remain incompletely characterized. This review synthesizes current advances in cilium-restricted receptor-type or membrane-bound GCs while systematically elucidating their functional specialization within the ciliary compartment.
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He et al. (2025) studied this question.
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