Animals sample their environment through sensory neurons with often elaborately branched endings named dendritic arbors. In a genetic screen for genes involved in the development of the highly arborized somatosensory PVD neuron in C. elegans, we have identified mutations in kpc-1, which encodes the homolog of the proprotein convertase furin. We show that kpc- 1/furin is necessary to promote the formation of higher order dendritic branches in PVD and to ensure self-avoidance of sister branches, but is likely not required during maintenance of dendritic arbors. A reporter for kpc-1/furin is expressed in neurons (including PVD) and kpc- 1/furin can function cell-autonomously in PVD neurons to control patterning of dendritic arbors. Moreover, we show that kpc- 1/furin also regulates the development of other neurons in all major neuronal classes in C. elegans, including aspects of branching and extension of neurites as well as cell positioning. Our data suggest that these developmental functions require proteolytic activity of KPC-1/furin. Recently, the skin-derived MNR-1/menorin and the neural cell adhesion molecule SAX-7/L1CAM have been shown to act as a tripartite complex with the leucine rich transmembrane receptor DMA-1 on PVD mechanosensory to orchestrate the patterning of dendritic branches. Genetic analyses show that kpc-1/furin functions in a pathway with MNR-1/menorin, SAX-7/L1CAM and DMA-1 to control dendritic branch formation and extension of PVD neurons. We propose that KPC-1/furin acts in concert with the ‘menorin’ pathway to control branching and growth of somatosensory dendrites in PVD.
Sensory neurons receive input from other neurons or sample their environment through elaborate structures termed dendritic trees. The correct patterning of dendritic trees is crucial for the proper function of the nervous system, and ample evidence points to the involvement of dendritic defects in a wide range of neuropsychiatric diseases. However, we still do not understand fully how this process is regulated at the molecular level. We discovered an important role for the protein-processing enzyme KPC-1/furin in the development of touch-sensitive dendritic trees in the roundworm C. elegans. Animals lacking this enzyme show multiple defects in the size, shape and number of these dendritic branches as well as other neurons. We further show that the gene encoding KPC-1 is expressed widely in the nervous system and that it is required within the branching neuron to exert its function on dendritic growth. Finally, we reveal a genetic connection between KPC-1 function and genes of the menorin pathway, which was recently discovered to also play an essential role in dendrite development. Thus, our findings add new insight into the molecular understanding of dendrite formation.