title: Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Howard Hughes Medical Institute and Rockefeller University, New York, NY 10065, USA. slbauerhuang@gmail.com
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Bauer Huang
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Saheki
authors.forename: Miri K
authors.initials: MK
authors.lastname: VanHoven
authors.forename: Ichiro
authors.initials: I
authors.lastname: Torayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Isao
authors.initials: I
authors.lastname: Katsura
authors.forename: Alexander
authors.initials: A
authors.lastname: van der Linden
authors.forename: Piali
authors.initials: P
authors.lastname: Sengupta
authors.forename: Cornelia I
authors.initials: CI
authors.lastname: Bargmann
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D062445:Claudin-1; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D007839:Functional Laterality / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D062445:Claudin-1; D017630:Connexins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C109164:Egl-19 protein, C elegans; D008565:Membrane Proteins; D009124:Muscle Proteins; C533258:OLRN-1 protein, C elegans; C115863:raw protein, Drosophila; C093204:unc-2 protein, C elegans; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2