title: Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function.
abstract: Reception and interpretation of environmental stimuli is critical for the survival of all organisms. Here, we show that the ablation of BBS1 and BBS4, two genes mutated in Bardet-Biedl syndrome and that encode proteins that localize near the centrioles of sensory neurons, leads to alterations of s.c. sensory innervation and trafficking of the thermosensory channel TRPV1 and the mechanosensory channel STOML3, with concomitant defects in peripheral thermosensation and mechanosensation. The thermosensory phenotype is recapitulated in Caenorhabditis elegans, because BBS mutants manifest deficient thermosensory responses at both physiological and nociceptive temperatures and defective trafficking of OSM-9, a polymodal sensory channel protein and a functional homolog of TRPV1 or TRPV4. Our findings suggest a hitherto unrecognized, but essential, role for mammalian basal body proteins in the acquisition of mechano- and thermosensory stimuli and highlight potentially clinical features of ciliopathies in humans.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Perciliz L
authors.initials: PL
authors.lastname: Tan
authors.forename: Travis
authors.initials: T
authors.lastname: Barr
authors.forename: Peter N
authors.initials: PN
authors.lastname: Inglis
authors.forename: Norimasa
authors.initials: N
authors.lastname: Mitsuma
authors.forename: Susan M
authors.initials: SM
authors.lastname: Huang
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Garcia-Gonzalez
authors.forename: Brian A
authors.initials: BA
authors.lastname: Bradley
authors.forename: Stephanie
authors.initials: S
authors.lastname: Coforio
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Albrecht
authors.forename: Terry
authors.initials: T
authors.lastname: Watnick
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Germino
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
authors.forename: Michel R
authors.initials: MR
authors.lastname: Leroux
authors.forename: Frank L
authors.initials: FL
authors.lastname: Rice
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D030801:Animals, Genetically Modified; D020788:Bardet-Biedl Syndrome / Q000378:metabolism / Q000473:pathology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013696:Temperature
chemical_list: D009419:Nerve Tissue Proteins