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 J. Caterina, Michel R. Leroux, Frank L. Rice, Nicholas Katsanis

Research output: Contribution to journalArticlepeer-review

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

Keywords

  • Basal bodies
  • Cilia
  • Thermosensation

ASJC Scopus subject areas

  • General

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