title: Kinesin-1 acts with netrin and DCC to maintain sensory neuron position in Caenorhabditis elegans.
abstract: The organization of neurons and the maintenance of that arrangement are critical to brain function. Failure of these processes in humans can lead to severe birth defects, mental retardation, and epilepsy. Several kinesins have been shown to play important roles in cell migration in vertebrate systems, but few upstream and downstream pathway members have been identified. Here, we utilize the genetic model organism Caenorhabditis elegans to elucidate the pathway by which the C. elegans Kinesin-1 Heavy Chain (KHC)/KIF5 ortholog UNC-116 functions to maintain neuronal cell body position in the PHB sensory neurons. We find that UNC-116/KHC acts in part with the cell and axon migration molecules UNC-6/Netrin and UNC-40/DCC in this process, but in parallel to SAX-3/Robo. We have also identified several potential adaptor, cargo, and regulatory proteins that may provide insight into the mechanism of UNC-116/KHC's function in this process. These include the cargo receptor UNC-33/CRMP2, the cargo adaptor protein UNC-76/FEZ and its regulator UNC-51/ULK, the cargo molecule UNC-69/SCOCO, and the actin regulators UNC-44/Ankyrin and UNC-34/Enabled. These genes also act in cell migration and axon outgrowth; however, many proteins that function in these processes do not affect PHB position. Our findings suggest an active posterior cell migration mediated by UNC-116/KHC occurs throughout development to maintain proper PHB cell body position and define a new pathway that mediates maintenance of neuronal cell body position.
authors.affiliation: Department of Biological Sciences, San José State University, San José, California 95192, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Barsi-Rhyne
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Miller
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Vargas
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Thomas
authors.forename: Joori
authors.initials: J
authors.lastname: Park
authors.forename: Martina
authors.initials: M
authors.lastname: Bremer
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Jarecki
authors.forename: Miri K
authors.initials: MK
authors.lastname: VanHoven
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075385:Netrins; D000091402:Prohibitins; D011971:Receptors, Immunologic / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D000097905:Roundabout Proteins
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D005346:Fibroblast Growth Factors; D016547:Kinesins; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D000091402:Prohibitins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C000717328:PHB protein, human; C502663:UNC-116 protein, C elegans; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans