The SAX-3 receptor stimulates axon outgrowth and the signal sequence and transmembrane domain are critical for SAX-3 membrane localization in the PDE neuron of C. elegans.

SAX-3, a receptor for Slit in C. elegans, is well characterized for its function in axonal development. However, the mechanism that regulates the membrane localization of SAX-3 and the role of SAX-3 in axon outgrowth are still elusive. Here we show that SAX-3::GFP caused ectopic axon outgrowth, which could be suppressed by the loss-of-function mutation in unc-73 (a guanine nucleotide exchange factor for small GTPases) and unc-115 (an actin binding protein), suggesting that they might act downstream of SAX-3 in axon outgrowth. We also examined genes related to axon development for their possible involvement in the subcellular localization of SAX-3. We found the unc-51 mutants appeared to accumulate SAX-3::GFP in the neuronal cell body of the posterior deirid (PDE) neuron, indicating that UNC-51 might play a role in SAX-3 membrane localization. Furthermore, we demonstrate that the N-terminal signal sequence and the transmembrane domain are essential for the subcellular localization of SAX-3 in the PDE neurons.