Physiological Condition-Dependent Changes in Ciliary GPCR Localization in the Brain.

Autor:	Brewer KM; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Engle SE; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Bansal R; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Brewer KK; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202., Jasso KR; Department of Neuroscience and Center for Smell and Taste, University of Florida, Gainesville, Florida 32603., McIntyre JC; Department of Neuroscience and Center for Smell and Taste, University of Florida, Gainesville, Florida 32603., Vaisse C; Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California 94143., Reiter JF; Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94158., Berbari NF; Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202 nberbari@iupui.edu.; Stark Neurosciences Research Institute, Indiana University, Indianapolis, Indiana 46202.; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2023 Mar 13; Vol. 10 (3). Date of Electronic Publication: 2023 Mar 13 (Print Publication: 2023).
DOI:	10.1523/ENEURO.0360-22.2023
Abstrakt:	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. Competing Interests: The authors declare no competing financial interests. (Copyright © 2023 Brewer et al.)
Databáze:	MEDLINE
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