The kpc-1 (furin) 3'UTR promotes dendritic transport and local translation of mRNAs to regulate dendrite branching and self-avoidance of a nociceptive neuron

A recently reported Schizophrenia-associated genetic variant in the 3UTR of the human furin gene, a homolog of C. elegans kpc-1, highlights an important role of the furin 3UTR in neuronal development(1). We isolate three kpc-1 mutants that display abnormal dendrite arborization in PVD neurons and defective male mating behaviors. We show that the kpc-1 3UTR participates in dendrite branching and self-avoidance. The kpc-1 3UTR facilitates mRNA localization to branching points and contact points between sibling dendrites and promotes local protein synthesis. We identify a secondary structural motif in the kpc-1 3UTR required for dendrite self-avoidance. Animals with dma-1 receptor over-expression exhibit similar dendrite branching and self-avoidance defects that are suppressed with kpc-1 over-expression. Our results support a model in which KPC-1 proteins are synthesized at branching points and contact points to locally down-regulate DMA-1 receptors to promote dendrite branching and self-avoidance of a mechanosensory neuron important for male courtship.