Loss of Bardet-Biedl syndrome proteins causes defects in peripheral sensory innervation and function

Perciliz L. Tan, Travis Barr, Peter N. Inglis, Norimasa Mitsuma, Susan M. Huang, Miguel A. Garcia-Gonzalez, Brian A. Bradley, Stephanie Coforio, Phillip J. Albrecht, Terry Watnick, Gregory G. Germino, Philip L. Beales, Michael Caterina, Michel R. Leroux, Frank L. Rice, Nicholas Katsanis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)17524-17529
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number44
DOIs
StatePublished - Oct 30 2007

Fingerprint

Bardet-Biedl Syndrome
Basal Bodies
Centrioles
Proteins
Caenorhabditis elegans
Sensory Receptor Cells
Phenotype
Temperature
Survival
Genes

Keywords

  • Basal bodies
  • Cilia
  • Thermosensation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Loss of Bardet-Biedl syndrome proteins causes defects in peripheral sensory innervation and function. / Tan, Perciliz L.; Barr, Travis; Inglis, Peter N.; Mitsuma, Norimasa; Huang, Susan M.; Garcia-Gonzalez, Miguel A.; Bradley, Brian A.; Coforio, Stephanie; Albrecht, Phillip J.; Watnick, Terry; Germino, Gregory G.; Beales, Philip L.; Caterina, Michael; Leroux, Michel R.; Rice, Frank L.; Katsanis, Nicholas.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 44, 30.10.2007, p. 17524-17529.

Research output: Contribution to journalArticle

Tan, PL, Barr, T, Inglis, PN, Mitsuma, N, Huang, SM, Garcia-Gonzalez, MA, Bradley, BA, Coforio, S, Albrecht, PJ, Watnick, T, Germino, GG, Beales, PL, Caterina, M, Leroux, MR, Rice, FL & Katsanis, N 2007, 'Loss of Bardet-Biedl syndrome proteins causes defects in peripheral sensory innervation and function', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 44, pp. 17524-17529. https://doi.org/10.1073/pnas.0706618104
Tan, Perciliz L. ; Barr, Travis ; Inglis, Peter N. ; Mitsuma, Norimasa ; Huang, Susan M. ; Garcia-Gonzalez, Miguel A. ; Bradley, Brian A. ; Coforio, Stephanie ; Albrecht, Phillip J. ; Watnick, Terry ; Germino, Gregory G. ; Beales, Philip L. ; Caterina, Michael ; Leroux, Michel R. ; Rice, Frank L. ; Katsanis, Nicholas. / Loss of Bardet-Biedl syndrome proteins causes defects in peripheral sensory innervation and function. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 44. pp. 17524-17529.
@article{73871430810746368fb8cd78cef7a801,
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.",
keywords = "Basal bodies, Cilia, Thermosensation",
author = "Tan, {Perciliz L.} and Travis Barr and Inglis, {Peter N.} and Norimasa Mitsuma and Huang, {Susan M.} and Garcia-Gonzalez, {Miguel A.} and Bradley, {Brian A.} and Stephanie Coforio and Albrecht, {Phillip J.} and Terry Watnick and Germino, {Gregory G.} and Beales, {Philip L.} and Michael Caterina and Leroux, {Michel R.} and Rice, {Frank L.} and Nicholas Katsanis",
year = "2007",
month = "10",
day = "30",
doi = "10.1073/pnas.0706618104",
language = "English (US)",
volume = "104",
pages = "17524--17529",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "44",

}

TY - JOUR

T1 - Loss of Bardet-Biedl syndrome proteins causes defects in peripheral sensory innervation and function

AU - Tan, Perciliz L.

AU - Barr, Travis

AU - Inglis, Peter N.

AU - Mitsuma, Norimasa

AU - Huang, Susan M.

AU - Garcia-Gonzalez, Miguel A.

AU - Bradley, Brian A.

AU - Coforio, Stephanie

AU - Albrecht, Phillip J.

AU - Watnick, Terry

AU - Germino, Gregory G.

AU - Beales, Philip L.

AU - Caterina, Michael

AU - Leroux, Michel R.

AU - Rice, Frank L.

AU - Katsanis, Nicholas

PY - 2007/10/30

Y1 - 2007/10/30

N2 - 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.

AB - 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.

KW - Basal bodies

KW - Cilia

KW - Thermosensation

UR - http://www.scopus.com/inward/record.url?scp=36849090468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36849090468&partnerID=8YFLogxK

U2 - 10.1073/pnas.0706618104

DO - 10.1073/pnas.0706618104

M3 - Article

C2 - 17959775

AN - SCOPUS:36849090468

VL - 104

SP - 17524

EP - 17529

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 44

ER -