title: Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans.
abstract: The axons of C. elegans left and right AWC olfactory neurons communicate at synapses through a calcium-signaling complex to regulate stochastic asymmetric cell identities called AWC(ON) and AWC(OFF). However, it is not known how the calcium-signaling complex, which consists of UNC-43/CaMKII, TIR-1/SARM adaptor protein and NSY-1/ASK1 MAPKKK, is localized to postsynaptic sites in the AWC axons for this lateral interaction. Here, we show that microtubule-based localization of the TIR-1 signaling complex to the synapses regulates AWC asymmetry. Similar to unc-43, tir-1 and nsy-1 loss-of-function mutants, specific disruption of microtubules in AWC by nocodazole generates two AWC(ON) neurons. Reduced localization of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons strongly correlates with the 2AWC(ON) phenotype in nocodazole-treated animals. We identified kinesin motor unc-104/kif1a mutants for enhancement of the 2AWC(ON) phenotype of a hypomorphic tir-1 mutant. Mutations in unc-104, like microtubule depolymerization, lead to a reduced level of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons. In addition, dynamic transport of TIR-1 in the AWC axons is dependent on unc-104, the primary motor required for the transport of presynaptic vesicles. Furthermore, unc-104 acts non-cell autonomously in the AWC(ON) neuron to regulate the AWC(OFF) identity. Together, these results suggest a model in which UNC-104 may transport some unknown presynaptic factor(s) in the future AWC(ON) cell that non-cell autonomously control the trafficking of the TIR-1 signaling complex to postsynaptic regions of the AWC axons to regulate the AWC(OFF) identity.
authors.affiliation: Division of Developmental Biology, Children's Hospital Medical Center Research Foundation, Cincinnati, OH 45229, USA.
authors.forename: Chieh
authors.initials: C
authors.lastname: Chang
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Bluma J
authors.initials: BJ
authors.lastname: Lesch
authors.forename: Cornelia I
authors.initials: CI
authors.lastname: Bargmann
authors.forename: Chiou-Fen
authors.initials: CF
authors.lastname: Chuang
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D018507:Gene Expression Regulation, Developmental; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D016547:Kinesins