Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia |
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Authors: | Berbari Nicolas F Lewis Jacqueline S Bishop Georgia A Askwith Candice C Mykytyn Kirk |
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Affiliation: | Departments of Pharmacology, Internal Medicine, Division of Human Genetics, and Neuroscience, College of Medicine, Ohio State University, Columbus, OH 43210, USA. |
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Abstract: | Primary cilia are ubiquitous cellular appendages that provide important yet not well understood sensory and signaling functions. Ciliary dysfunction underlies numerous human genetic disorders. However, the precise defects in cilia function and the basis of disease pathophysiology remain unclear. Here, we report that the proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localization of G protein-coupled receptors to primary cilia on central neurons. We demonstrate a lack of ciliary localization of somatostatin receptor type 3 (Sstr3) and melanin-concentrating hormone receptor 1 (Mchr1) in neurons from mice lacking the Bbs2 or Bbs4 gene. Because Mchr1 is involved in the regulation of feeding behavior and BBS is associated with hyperphagia-induced obesity, our results suggest that altered signaling caused by mislocalization of ciliary signaling proteins underlies the BBS phenotypes. Our results also provide a potential molecular mechanism to link cilia defects with obesity. |
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Keywords: | melanin-concentrating hormone receptor 1 neuronal cilia obesity somatostatin receptor 3 type III adenylyl cyclase |
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