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 AWCOFF and induced AWCON. 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 AWCOFF subtype through lateral signaling. UNC-104, the C. elegans homolog of the kinesin-3 motor protein KIF1A, acts non-cell autonomously in AWCON to control the synaptic localization of the TIR-1 signaling complex in promoting AWCOFF. Here, we identify a non-cell-autonomous role of unc-116/kinesin-1, similar to that of unc-104/kinesin-3, in promoting AWCOFF. unc-116 mutants, similar to unc-104 mutants, enhance the 2AWCON phenotype of a hypomorphic tir-1 mutant. Overexpression of unc-116 in AWC causes a 2AWCOFF phenotype, the same as the tir-1 overexpression phenotype. Like UNC-104, UNC-116 plays a non-cell-autonomous role in the AWCON cell to promote AWCOFF 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 AWCON 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 AWCOFF subtype.