The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates.
A stochastic cell fate decision mediated by axon contact and calcium signaling causes one of the two bilaterally symmetric AWC neurons, either AWCL or AWCR, to express the candidate olfactory receptor str-2. nsy-1 mutants express str-2 in both neurons, disrupting AWC asymmetry. nsy-1 encodes a homolog of the human MAP kinase kinase kinase (MAPKKK) ASK1, an activator of JNK and p38 kinases. Based on genetic epistasis analysis, nsy-1 appears to act downstream of the CaMKII unc-43, and NSY-1 associates with UNC-43, suggesting that UNC-43/CaMKII activates the NSY-1 MAP kinase cassette. Mosaic analysis demonstrates that UNC-43 and NSY-1 act primarily in a cell-autonomous execution step that represses str-2 expression in one AWC cell, downstream of the initial lateral signaling pathway that coordinates the fates of the two cells.
Sagasti
A
A
Howard Hughes Medical Institute, Programs in Developmental Biology, Neuroscience, and Genetics, Department of Anatomy and Department of, Biochemistry and Biophysics, The University of California, San Francisco, San Francisco, CA 94143, USA.
Hisamoto
N
N
Hyodo
J
J
Tanaka-Hino
M
M
Matsumoto
K
K
Bargmann
C I
CI
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004843:Epistasis, Genetic; D018390:Gene Targeting; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009030:Mosaicism / Q000235:genetics*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D010766:Phosphorylation; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D019076:Transgenes / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D018035:Receptors, Odorant; D011993:Recombinant Fusion Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517679:unc-43 protein, C elegans; D020930:MAP Kinase Kinase Kinases