1. Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans
- Author
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Yasunori Saheki, Miri K. VanHoven, Sarah L. Bauer Huang, Ichiro Torayama, Alexander M. van der Linden, Isao Katsura, Piali Sengupta, Takeshi Ishihara, and Cornelia I. Bargmann
- Subjects
Sensory Receptor Cells ,MAP Kinase Signaling System ,Cellular differentiation ,Muscle Proteins ,chemistry.chemical_element ,Calcium ,Biology ,Nervous System ,Connexins ,Functional Laterality ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,Ca2+/calmodulin-dependent protein kinase ,Claudin-1 ,medicine ,Animals ,Drosophila Proteins ,Calcium Signaling ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Calcium signaling ,0303 health sciences ,Voltage-dependent calcium channel ,Calcium channel ,Gene Expression Regulation, Developmental ,Membrane Proteins ,Cell Differentiation ,Olfactory Pathways ,biology.organism_classification ,Cell biology ,Cytoskeletal Proteins ,medicine.anatomical_structure ,chemistry ,Calcium Channels ,Neuron ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,030217 neurology & neurosurgery ,Research Article - 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.
- Published
- 2007