Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function.
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.
Tan
Perciliz L
PL
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Barr
Travis
T
Inglis
Peter N
PN
Mitsuma
Norimasa
N
Huang
Susan M
SM
Garcia-Gonzalez
Miguel A
MA
Bradley
Brian A
BA
Coforio
Stephanie
S
Albrecht
Phillip J
PJ
Watnick
Terry
T
Germino
Gregory G
GG
Beales
Philip L
PL
Caterina
Michael J
MJ
Leroux
Michel R
MR
Rice
Frank L
FL
Katsanis
Nicholas
N
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
D009419:Nerve Tissue Proteins