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PMID: 18334641 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 11 ·2008-03-18 ·Pages 4242-6

Berbari NF, Lewis JS, Bishop GA, Askwith CC, Mykytyn K

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.

MeSH Terms
Animals Bardet-Biedl Syndrome/genetics,metabolism Cells, Cultured Cilia/metabolism Mice Mice, Knockout Microtubule-Associated Proteins/deficiency,genetics,metabolism Mutation/genetics Proteins/genetics,metabolism Receptors, Somatostatin/metabolism
Chemicals
BBS4 protein, mouse Bbs2 protein, mouse Mchr1 protein, mouse Microtubule-Associated Proteins Proteins Receptors, Somatostatin somatostatin receptor 3
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Berbari Nicolas F
Departments of Pharmacology, Internal Medicine, Division of Human Genetics, and Neuroscience, College of Medicine, Ohio State University, Columbus, OH 43210, USA.
Lewis Jacqueline S
Bishop Georgia A
Askwith Candice C
Mykytyn Kirk
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0711027105
Published
2008-03-18
Epub
2008-00-11
Pages
4242-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2393805
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0711027105 PMC Full Text View journal details
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