Prefix: : Prefix: i: Prefix: dc: Prefix: owl: Prefix: rdf: Prefix: xml: Prefix: xsd: Prefix: rdfs: Ontology: Import: Import: Import: Import: Annotations: rdfs:comment "PMID 21771813 Microtubule-based localization of a synaptic calcium- signaling complex is required for left-right neuronal asymmetry in C. elegans Chieh Chang1, Yi-Wen Hsieh1, Bluma J. Lesch2, Cornelia I. Bargmann2 and Chiou-Fen Chuang1,* SUMMARY 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 AWCON and AWCOFF. 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 AWCON neurons. Reduced localization of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons strongly correlates with the 2AWCON phenotype in nocodazole-treated animals. We identified kinesin motor unc-104/kif1a mutants for enhancement of the 2AWCON 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 AWCON neuron to regulate the AWCOFF identity. Together, these results suggest a model in which UNC-104 may transport some unknown presynaptic factor(s) in the future AWCON cell that non-cell autonomously control the trafficking of the TIR-1 signaling complex to postsynaptic regions of the AWC axons to regulate the AWCOFF identity." AnnotationProperty: rdfs:label AnnotationProperty: rdfs:comment Datatype: rdf:PlainLiteral ObjectProperty: BFO_0000066 ObjectProperty: directly_activates ObjectProperty: RO_0002212 ObjectProperty: RO_0002213 ObjectProperty: has_input ObjectProperty: has_output ObjectProperty: indirectly_disables_action_of ObjectProperty: enabled_by ObjectProperty: occurs_in ObjectProperty: activates ObjectProperty: BFO_0000050 ObjectProperty: directly_inhibits Class: WBbt_0005672 Class: GO_0019901 Class: GO_0030424 Class: UniProtKB_E0AHC6 Class: GO_0001078 Class: UniProtKB_H2KYW5 Class: GO_0030182 Class: GO_0034613 Class: UniProtKB_Q965R3 Class: UniProtKB_Q9N419 Class: UniProtKB_G5EDF7 Class: UniProtKB_P23678 Class: GO_0045596 Class: GO_0003700 Class: GO_0004871 Class: GO_0030154 Class: UniProtKB_O61715 Class: UniProtKB_O62305 Class: GO_0001708 Class: GO_0005634 Class: GO_0048675 Class: GO_0004709 Class: GO_0004708 Class: WBbt_0003826 Class: WBbt_0003827 Class: UniProtKB_G4SFC3 Class: GO_0005515 Class: UniProtKB_Q21029 Class: GO_0005200 Class: GO_0003777 Class: UniProtKB_Q86DA5 Class: GO_0004672 Class: GO_0032092 Class: GO_0060581 Class: GO_0004674 Class: GO_0035545 Class: GO_0005243 SubClassOf: occurs_in some GO_0005921 Class: GO_0003674 Class: GO_0005262 Class: GO_0005923 Class: GO_0060573 Class: UniProtKB_Q18817 Class: GO_0005921 Class: UniProtKB_G5EF54 Class: GO_0016337 Class: GO_0015267 Class: WBbt_0005832 Class: WBbt_0005833 Individual: DPH_4000010 Annotations: rdfs:label "unc-2-calcium channel activity in AWC-ON" Types: GO_0005262, enabled_by some UniProtKB_G4SFC3, BFO_0000066 some WBbt_0005832 Individual: DPH_4000012 Annotations: rdfs:label "microtubule organization in AWC-OFF" Types: GO_0005200, enabled_by some UniProtKB_Q18817 Facts: BFO_0000050 DPH_4000003 Individual: DPH_4000011 Annotations: rdfs:label "AWC axon outgrowth" Types: BFO_0000066 some WBbt_0005672, GO_0048675 Individual: LEGO_PMID_21771813_0000016 Annotations: rdfs:label "unc-76 activity"@en Types: GO_0004871, enabled_by some UniProtKB_E0AHC6, BFO_0000066 some WBbt_0003827, BFO_0000066 some GO_0030424 Facts: directly_activates LEGO_PMID_21771813_0000024, directly_activates LEGO_PMID_21771813_0000023, BFO_0000050 DPH_4000011, BFO_0000050 DPH_4000001 Individual: LEGO_PMID_21771813_0000019 Annotations: rdfs:label "nsy-1-MAPKKK activity"@en Types: BFO_0000066 some WBbt_0003827, BFO_0000066 some GO_0030424, GO_0004674, enabled_by some UniProtKB_Q21029 Facts: directly_activates LEGO_PMID_21771813_0000018, BFO_0000050 DPH_4000003 Individual: LEGO_PMID_21771813_0000018 Annotations: rdfs:label "sek-1-MAPKK-activity"@en Types: GO_0004674, enabled_by some UniProtKB_G5EDF7 Facts: directly_activates LEGO_PMID_21771813_0000026, directly_inhibits LEGO_PMID_21771813_0000025, BFO_0000050 DPH_4000004, BFO_0000050 DPH_4000003 Individual: DPH_4000005 Annotations: rdfs:label "srsx-3 -> AWC-OFF" Types: occurs_in some WBbt_0005833, enabled_by some UniProtKB_Q965R3, GO_0003674 Facts: BFO_0000050 DPH_4000004 Individual: DPH_4000004 Annotations: rdfs:label "negative regulation of AWC-ON differentiation in AWC-OFF cell" Types: occurs_in some WBbt_0005833, GO_0045596 Facts: RO_0002212 DPH_4000007 Individual: DPH_4000007 Annotations: rdfs:label "AWC-ON cell differentiation from AWCR" Types: GO_0030182, has_input some WBbt_0003826, has_output some WBbt_0005832 Individual: DPH_4000006 Annotations: rdfs:label "AWC-OFF cell differentiation from AWCL" Types: GO_0030182, has_output some WBbt_0005833, has_input some WBbt_0003827 Individual: DPH_4000009 Annotations: rdfs:label "axonal localization of Unc-43, NSY-1, TIR-1" Types: BFO_0000066 some WBbt_0003827, BFO_0000066 some GO_0030424, GO_0034613 Individual: DPH_4000008 Annotations: rdfs:label "unc-104 activity" Types: BFO_0000066 some WBbt_0003826, GO_0003777, enabled_by some UniProtKB_P23678 Facts: BFO_0000050 DPH_4000003, BFO_0000050 DPH_4000009 Individual: DPH_4000001 Annotations: rdfs:label "negative regulation of AWC-OFF differentiation in AWC-ON cell" Types: occurs_in some WBbt_0005832, GO_0045596 Facts: RO_0002212 DPH_4000006 Individual: DPH_4000000 Annotations: rdfs:label "nsy-7 as transcription repressor of srsx-3" Types: enabled_by some UniProtKB_H2KYW5, occurs_in some WBbt_0005833, occurs_in some GO_0005634, GO_0001078 Facts: BFO_0000050 DPH_4000001, RO_0002212 DPH_4000005 Individual: DPH_4000003 Annotations: rdfs:label "cell fate commitment of AWC-OFF cell" Types: occurs_in some WBbt_0003827, GO_0060581, has_output some WBbt_0005833 Facts: BFO_0000050 DPH_4000006, BFO_0000050 LEGO_PMID_21771813_0000027 Individual: DPH_4000002 Annotations: rdfs:label "cell fate specification of AWC-ON cell" Types: occurs_in some WBbt_0003826, GO_0060581, has_output some WBbt_0005832 Facts: BFO_0000050 DPH_4000007, BFO_0000050 LEGO_PMID_21771813_0000027 Individual: LEGO_PMID_21771813_0000020 Annotations: rdfs:label "tir-1 activity"@en, rdfs:comment "Here, we show that microtubule-based localization of the TIR-1 signaling complex to the synapses regulates AWC asymmetry" Types: GO_0019901, BFO_0000050 some GO_0032092, enabled_by some UniProtKB_Q86DA5 Facts: directly_activates LEGO_PMID_21771813_0000021, directly_activates LEGO_PMID_21771813_0000019, BFO_0000050 DPH_4000003 Individual: LEGO_PMID_21771813_0000024 Annotations: rdfs:label "claudin activity"@en, rdfs:comment "establishment of cell fate?" Types: GO_0005515, BFO_0000066 some WBbt_0003826, enabled_by some UniProtKB_Q9N419, occurs_in some GO_0005923, BFO_0000050 some GO_0016337 Facts: BFO_0000050 DPH_4000001, directly_inhibits DPH_4000010 Individual: LEGO_PMID_21771813_0000023 Annotations: rdfs:label "innexin activity"@en, rdfs:comment "establishment of cell fate?" Types: BFO_0000066 some WBbt_0003826, GO_0005243, enabled_by some UniProtKB_O61715 Facts: BFO_0000050 DPH_4000001, directly_inhibits DPH_4000010 Individual: LEGO_PMID_21771813_0000022 Annotations: rdfs:label "unc-2-calcium channel activity in AWC-OFF"@en Types: GO_0005262, BFO_0000066 some WBbt_0003827, enabled_by some UniProtKB_G4SFC3 Facts: directly_activates LEGO_PMID_21771813_0000021, BFO_0000050 DPH_4000003 Individual: LEGO_PMID_21771813_0000021 Annotations: rdfs:label "CaMKII/UNC-43 activity"@en Types: enabled_by some UniProtKB_O62305, BFO_0000066 some WBbt_0003827, GO_0004672, BFO_0000066 some GO_0030424 Facts: BFO_0000050 DPH_4000003, directly_activates LEGO_PMID_21771813_0000019 Individual: LEGO_PMID_21771813_0000028 Annotations: rdfs:comment "check: no 'maintenance of cell identity' in GO. Existing GO annotation is to 'neuron fate specification'. GO:0001708 ! cell fate specification [DEF: \"The process involved in the specification of cell identity. Once specification has taken place, a cell will be committed to differentiate down a specific pathway if left in its normal environment.\"]", rdfs:label "nsy-7 activity"@en, rdfs:comment "NSY-7 likely acts as a transcriptional regulator that represses expression of AWC-OFF genes, such as srsx-3 and hlh-11, in the AWC-ON cell; in vitro, NSY-7 displays sequence-specific, DNA-binding activity to elements found within the promoter regions of srsx-3 and hlh-11; consistent with its role as a transcriptional regulator, a NSY-7::GFP reporter localizes to the AWC nucleus" Types: enabled_by some UniProtKB_H2KYW5, GO_0003674, BFO_0000066 some WBbt_0005832 Facts: RO_0002213 LEGO_PMID_21771813_0000025, BFO_0000050 DPH_4000002 Individual: LEGO_PMID_21771813_0000027 Annotations: rdfs:label "l/r asymmetry"@en Types: GO_0035545 Individual: LEGO_PMID_21771813_0000026 Annotations: rdfs:label "srsx-3 -> AWCL"@en, rdfs:comment "Troemel et al. 1999; Bauer Huang et al. 2007" Types: BFO_0000066 some WBbt_0003827, enabled_by some UniProtKB_Q965R3, GO_0003674 Facts: BFO_0000050 DPH_4000006 Individual: LEGO_PMID_21771813_0000025 Annotations: rdfs:label "str-2 -> AWC-ON"@en, rdfs:comment "Troemel et al. 1999; Bauer Huang et al. 2007" Types: occurs_in some WBbt_0005832, enabled_by some UniProtKB_G5EF54, GO_0003674 Facts: BFO_0000050 DPH_4000001, BFO_0000050 DPH_4000007