The blind leading the obese: the molecular pathophysiology of a human obesity syndrome.
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder affecting multiple organ systems and resulting in blindness, obesity, cognitive impairment, and congenital defects. Interest in the etiology of this disorder stems, in part, from the fact that patients with BBS develop common clinical problems, including obesity, diabetes and hypertension. Twelve genes independently causing BBS have been identified. The heterogeneity is explained by the existence of two BBS complexes, the BBSome consisting of seven known BBS proteins, and the BBS chaperone complex consisting of three known BBS proteins. The formation of the BBSome requires the function of the BBS chaperone complex. Both mouse and zebrafish data support a role for BBS genes in cilia function, and in intracellular and intraflagellar trafficking. From the work described here, a common primary function of BBS proteins has emerged, specifically the mediation and regulation of microtubule-based intracellular transport.
Sheffield
Val C
VC
Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, 4181 MERF, University of Iowa Iowa City, IA 52242, USA. val-sheffield@uiowa.edu
D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000503:physiopathology*; D001766:Blindness / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D015027:Zebrafish
C506281:BBS4 protein, mouse; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes