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

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.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.Olfactory neurons sense environmental chemicals using large families of chemoreceptor genes that are deployed in elaborate patterns. For example, the main olfactory organs of the nematode Caenorhabditis elegans are the bilateral (left and right) amphids, which house 12 pairs of ciliated sensory neurons. Each sensory neuron expresses many receptor genes, in contrast with vertebrate olfactory neurons that generally express one receptor gene per cell [1]. Every neuron pair expresses a unique complement of receptors, and in addition, expression of some receptor genes is asymmetric on the left and right sides. For example, the left and right ASE gustatory neurons (ASEL and ASER) are structurally similar, but they express different receptor genes a