Open Access Research article

Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans

Sarah L Bauer Huang12, Yasunori Saheki1, Miri K VanHoven12, Ichiro Torayama3, Takeshi Ishihara3, Isao Katsura3, Alexander van der Linden4, Piali Sengupta4 and Cornelia I Bargmann1*

Author Affiliations

1 Howard Hughes Medical Institute and Rockefeller University, New York, NY 10065, USA

2 Herbert W Boyer Program in Biological Sciences, The University of California, San Francisco, San Francisco, CA 94143, USA

3 Structural Biology Center, National Institute of Genetics, and Department of Genetics, The Graduate University for Advanced Studies, Mishima, 411-8540, Japan

4 Department of Biology and National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA

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Neural Development 2007, 2:24  doi:10.1186/1749-8104-2-24

Published: 6 November 2007

Abstract

Background

The left and right AWC olfactory neurons in Caenorhabditis elegans differ in their functions and in their expression of chemosensory receptor genes; in each animal, one AWC randomly takes on one identity, designated AWCOFF, and the contralateral AWC becomes AWCON. Signaling between AWC neurons induces left-right asymmetry through a gap junction network and a claudin-related protein, which inhibit a calcium-regulated MAP kinase pathway in the neuron that becomes AWCON.

Results

We show here that the asymmetry gene olrn-1 acts downstream of the gap junction and claudin genes to inhibit the calcium-MAP kinase pathway in AWCON. OLRN-1, a protein with potential membrane-association domains, is related to the Drosophila Raw protein, a negative regulator of JNK mitogen-activated protein (MAP) kinase signaling. olrn-1 opposes the action of two voltage-activated calcium channel homologs, unc-2 (CaV2) and egl-19 (CaV1), which act together to stimulate the calcium/calmodulin-dependent kinase CaMKII and the MAP kinase pathway. Calcium channel activity is essential in AWCOFF, and the two AWC neurons coordinate left-right asymmetry using signals from the calcium channels and signals from olrn-1.

Conclusion

olrn-1 and voltage-activated calcium channels are mediators and targets of AWC signaling that act at the transition between a multicellular signaling network and cell-autonomous execution of the decision. We suggest that the asymmetry decision in AWC results from the intercellular coupling of voltage-regulated channels, whose cross-regulation generates distinct calcium signals in the left and right AWC neurons. The interpretation of these signals by the kinase cascade initiates the sustained difference between the two cells.