Reference - Detail
|Author||Bauer Huang SL, Saheki Y, VanHoven MK, Torayama I, Ishihara T, Katsura I, van der Linden A, Sengupta P, Bargmann CI.|
|Title||Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans.|
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.
|MeSH||Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / isolation & purification Caenorhabditis elegans Proteins / metabolism* Calcium Channels / genetics Calcium Channels / metabolism* Calcium Signaling / physiology Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism Cell Differentiation / genetics Claudin-1 Connexins / genetics Connexins / metabolism Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Functional Laterality / genetics* Gene Expression Regulation, Developmental / genetics MAP Kinase Signaling System / physiology Membrane Proteins / genetics Membrane Proteins / isolation & purification Membrane Proteins / metabolism* Muscle Proteins / genetics Muscle Proteins / metabolism Nervous System / cytology Nervous System / growth & development* Nervous System / metabolism Olfactory Pathways / cytology Olfactory Pathways / growth & development* Olfactory Pathways / metabolism Sensory Receptor Cells / cytology Sensory Receptor Cells / metabolism|