Regulation of Polarized Protein Transport to Axons, Dendrites, and Sensory Cilia in Caeborhabditis Elegans Neurons

Three proteins implicated in apparently distinct aspects of axon differentiation are the microtubule-binding protein CRMP, which promotes axon specification, the kinesin UNC104/Kif1A, which directs axonal traffic, and ankyrinG, which prevents dendritic protein diffusion into axons. The relationships among these molecules are unknown. We show here that the C. elegans CRMP homolog UNC-33 and ankyrin homolog UNC-44 act together to establish asymmetric sorting signals for both axons and dendrites. UNC-33 is localized to axons by UNC-44, and enriched in an axon segment near the cell body that suggests analogies with the vertebrate axon initial segment. In unc-33 and unc-44 mutants, axonal proteins are distributed randomly between axons and dendrites, dendritic proteins are partly localized to axons, and the distinctive organization of axonal and dendritic microtubules is disrupted. Dendrite integrity is corrupted by misregulated UNC104/KIF1A, which actively transports axonal proteins to dendrites. Although homologs of UNC-33 and UNC-44 are known to affect axons, the unexpected effects on dendrites suggest a broader function on asymmetric traffic. We propose that microtubules organized by UNC-33 capture the axonal motor UNC-104 to segregate axonal and dendritic sorting