RT Journal Article SR Electronic T1 Physiological Condition-Dependent Changes in Ciliary GPCR Localization in the Brain JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0360-22.2023 DO 10.1523/ENEURO.0360-22.2023 VO 10 IS 3 A1 Kathryn M. Brewer A1 Staci E. Engle A1 Ruchi Bansal A1 Katlyn K. Brewer A1 Kalene R. Jasso A1 Jeremy C. McIntyre A1 Christian Vaisse A1 Jeremy F. Reiter A1 Nicolas F. Berbari YR 2023 UL http://www.eneuro.org/content/10/3/ENEURO.0360-22.2023.abstract AB Primary cilia are cellular appendages critical for diverse types of Signaling. They are found on most cell types, including cells throughout the CNS. Cilia preferentially localize certain G-protein-coupled receptors (GPCRs) and are critical for mediating the signaling of these receptors. Several of these neuronal GPCRs have recognized roles in feeding behavior and energy homeostasis. Cell and model systems, such as Caenorhabditis elegans and Chlamydomonas, have implicated both dynamic GPCR cilia localization and cilia length and shape changes as key for signaling. It is unclear whether mammalian ciliary GPCRs use similar mechanisms in vivo and under what conditions these processes may occur. Here, we assess two neuronal cilia GPCRs, melanin-concentrating hormone receptor 1 (MCHR1) and neuropeptide-Y receptor 2 (NPY2R), as mammalian model ciliary receptors in the mouse brain. We test the hypothesis that dynamic localization to cilia occurs under physiological conditions associated with these GPCR functions. Both receptors are involved in feeding behaviors, and MCHR1 is also associated with sleep and reward. Cilia were analyzed with a computer-assisted approach allowing for unbiased and high-throughput analysis. We measured cilia frequency, length, and receptor occupancy. We observed changes in ciliary length, receptor occupancy, and cilia frequency under different conditions for one receptor but not another and in specific brain regions. These data suggest that dynamic cilia localization of GPCRs depends on properties of individual receptors and cells where they are expressed. A better understanding of subcellular localization dynamics of ciliary GPCRs could reveal unknown molecular mechanisms regulating behaviors like feeding.