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PNAS 108 (1): 254-259

Copyright © 2011 by the National Academy of Sciences.


Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans

Elissa A. Hallema,1, W. Clay Spencerb, Rebecca D. McWhirterb, Georg Zellerc,d,2, Stefan R. Henzd, Gunnar Rätschc, David M. Miller, IIIb, H. Robert Horvitze, Paul W. Sternberga,3, and Niels Ringstade,f,3

aHoward Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, CA 91125; bDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232; c Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany; dDepartment of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany; eHoward Hughes Medical Institute, Department of Biology and McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; and fDepartment of Cell Biology and the Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York NY 10016

Contributed by Paul W. Sternberg, November 22, 2010 (sent for review August 2, 2010)

Abstract: CO2 is both a critical regulator of animal physiology and an important sensory cue for many animals for host detection, food location, and mate finding. The free-living soil nematode Caenorhabditis elegans shows CO2 avoidance behavior, which requires a pair of ciliated sensory neurons, the BAG neurons. Using in vivo calcium imaging, we show that CO2 specifically activates the BAG neurons and that the CO2-sensing function of BAG neurons requires TAX-2/TAX-4 cyclic nucleotide-gated ion channels and the receptor-type guanylate cyclase GCY-9. Our results delineate a molecular pathway for CO2 sensing and suggest that activation of a receptor-type guanylate cyclase is an evolutionarily conserved mechanism by which animals detect environmental CO2.

Key Words: guanylyl cyclase • olfaction • transcriptional profiling • regulator of G protein signaling • chemosensation

Freely available online through the PNAS open access option.

Author contributions: E.A.H., D.M.M., H.R.H., P.W.S., and N.R. designed research; E.A.H., N.R., W.C.S., and R.D.M. performed research; E.A.H., G.Z., S.R.H., G.R., and N.R. analyzed data; and E.A.H., H.R.H., P.W.S., and N.R. wrote the paper.

1Present address: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095.

2Present address: Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.

The authors declare no conflict of interest.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. HQ636455). The gene expression data have been deposited in the Gene Expression Omnibus database (accession no. GSE23769).

This article contains supporting information online at

3To whom correspondence may be addressed. E-mail: pws{at} or niels.ringstad{at}

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