title: The proprotein convertase KPC-1/furin controls branching and self-avoidance of sensory dendrites in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, United States of America.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Salzberg
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, United States of America.
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Ramirez-Suarez
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, United States of America; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, United States of America.
authors.forename: Hannes E
authors.initials: HE
authors.lastname: Bülow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D045683:Furin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011984:Sensory Receptor Cells / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D029742:Caenorhabditis elegans Proteins; D045683:Furin