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

Neural Dev. 2007 Nov 6;2:24. doi: 10.1186/1749-8104-2-24.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

  • Caenorhabditis elegans Proteins
  • Calcium Channels
  • Claudin-1
  • Connexins
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Egl-19 protein, C elegans
  • Membrane Proteins
  • Muscle Proteins
  • OLRN-1 protein, C elegans
  • raw protein, Drosophila
  • unc-2 protein, C elegans
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2