title: Hyperactive neuroendocrine secretion causes size, feeding, and metabolic defects of C. elegans Bardet-Biedl syndrome mutants.
abstract: Bardet-Biedl syndrome, BBS, is a rare autosomal recessive disorder with clinical presentations including polydactyly, retinopathy, hyperphagia, obesity, short stature, cognitive impairment, and developmental delays. Disruptions of BBS proteins in a variety of organisms impair cilia formation and function and the multi-organ defects of BBS have been attributed to deficiencies in various cilia-associated signaling pathways. In C. elegans, bbs genes are expressed exclusively in the sixty ciliated sensory neurons of these animals and bbs mutants exhibit sensory defects as well as body size, feeding, and metabolic abnormalities. Here we show that in contrast to many other cilia-defective mutants, C. elegans bbs mutants exhibit increased release of dense-core vesicles and organism-wide phenotypes associated with enhanced activities of insulin, neuropeptide, and biogenic amine signaling pathways. We show that the altered body size, feeding, and metabolic abnormalities of bbs mutants can be corrected to wild-type levels by abrogating the enhanced secretion of dense-core vesicles without concomitant correction of ciliary defects. These findings expand the role of BBS proteins to the regulation of dense-core-vesicle exocytosis and suggest that some features of Bardet-Biedl Syndrome may be caused by excessive neuroendocrine secretion.
authors.affiliation: Department of Physiology and the UCSF Diabetes Center, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Lee
authors.forename: Jason
authors.initials: J
authors.lastname: Liu
authors.forename: Daisy
authors.initials: D
authors.lastname: Wong
authors.forename: Supriya
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Kaveh
authors.initials: K
authors.lastname: Ashrafi
mesh_terms: D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000503:physiopathology*; D049628:Body Size / Q000235:genetics*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002460:Cell Line; D002923:Cilia / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012701:Serotonin / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; C114560:Flp-1 protein, C elegans; D007328:Insulin; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D012701:Serotonin; C418215:IDA-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases