Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia.
Proc Natl Acad Sci U S A
; 105(11): 4242-6, 2008 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-18334641
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Cílios
/
Receptores de Somatostatina
/
Síndrome de Bardet-Biedl
/
Proteínas Associadas aos Microtúbulos
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos