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

Elissa A. Hallem^a,1, W. Clay Spencer^b, Rebecca D. McWhirter^b, Georg Zeller^c,d,2, Stefan R. Henz^d, Gunnar Rätsch^c, David M. Miller, III^b, H. Robert Horvitz^e, Paul W. Sternberg^a,3, and Niels Ringstad^e,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

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

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 www.pnas.org/lookup/suppl/doi:10.1073/pnas.1017354108/-/DCSupplemental.

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

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