Kinesin-1 trans-synaptically regulates synaptic localization of SARM1 for asymmetric neuron diversification

Abstract The Caenorhabditis elegans AWC olfactory neuron pair differentiates stochastically into two distinct subtypes, default AWC OFF and induced AWC ON . A calcium signaling complex assembled by the TIR-1/SARM1 adaptor protein is transported from the AWC cell body to the axons, where it cell autonomously specifies the AWC OFF subtype through lateral signaling. UNC-104, the C. elegans homolog of the kinesin-3 motor protein KIF1A, acts non-cell autonomously in AWC ON to control the synaptic localization of the TIR-1 signaling complex in promoting AWC OFF . Here, we identify a non-cell-autonomous role of unc-116/kinesin-1 , similar to that of unc-104/kinesin-3 , in promoting AWC OFF . unc-116 mutants, similar to unc-104 mutants, enhance the 2AWC ON phenotype of a hypomorphic tir-1 mutant. Overexpression of unc-116 in AWC causes a 2AWC OFF phenotype, the same as the tir-1 overexpression phenotype. Like UNC-104, UNC-116 plays a non-cell-autonomous role in the AWC ON cell to promote AWC OFF cell subtype by regulating the dynamic trafficking of TIR-1 along the AWC axon. UNC-116 is strikingly colocalized with UNC-104, while both are generally adjacent to TIR-1. Taken together, these results suggest a model in which UNC-116/kinesin-1 and UNC-104/kinesin-3 may work cooperatively to transport some unknown presynaptic factor(s) in the future AWC ON cell that trans-synaptically regulates the dynamic trafficking of the TIR-1/SARM1 signaling complex to postsynaptic regions of the AWC axons in promoting the AWC OFF subtype.