Non-motile primary cilia are sensory organelles that present in most vertebrate cell types. Its localization within tissue architecture and a growing list of cilia-localized receptors, in particular a limited set of G-protein-coupled receptors (GPCRs), determine a host of crucial physiologies, which are disrupted in human ciliopathies. Melanin-concentrating hormone (MCH) is a cyclic neuropeptide exerting its action through two GPCRs, MCHR1 and MCHR2. The extensive progress using genetic and pharmacological approaches has confirmed that the MCH-MCHR1 system is involved in feeding and possibly emotional processing. We recently found the that MCH signaling through a Gi/o-Akt pathway induces cilia length shortening in ciliary MCHR1-expressing RPE1 cells without no cell cycle progression. This is the first example of effective-neuropeptide-induced cilia length reduction. Here, we discuss our recent progress in the characterization of signaling components that cause cilia shortening via ciliary MCHR1 localized in neuron. Short cilia phenotypes have been associated with various metabolic disorders. Thus, our study has highlighted the unique signaling environment of the primary cilium, in which the design allows for organized signaling in neuronal network toward feeding.

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