The KLP-6 kinesin is required for male mating behaviors and polycystin localization in Caenorhabditis elegans.
BACKGROUND
Male mating behavior of the nematode Caenorhabditis elegans offers an intriguing model to study the genetics of sensory behavior, cilia function, and autosomal dominant polycystic kidney disease (ADPKD). The C. elegans polycystins LOV-1 and PKD-2 act in male-specific sensory cilia required for response and vulva-location mating behaviors.


RESULTS
Here, we identify and characterize a new mating mutant, sy511. sy511 behavioral phenotypes were mapped to a mutation in the klp-6 locus, a gene encoding a member of the kinesin-3 family (previously known as the UNC-104/Kif1A family). KLP-6 has a single homolog of unknown function in vertebrate genomes, including fish, chicken, mouse, rat, and human. We show that KLP-6 expresses exclusively in sensory neurons with exposed ciliated endings and colocalizes with the polycystins in cilia of male-specific neurons. Cilia of klp-6 mutants appear normal, suggesting a defect in sensory neuron function but not development. KLP-6 structure-function analysis reveals that the putative cargo binding domain directs the motor to cilia. Consistent with a motor-cargo association between KLP-6 and the polycystins, klp-6 is required for PKD-2 localization and function within cilia. Genetically, we find klp-6 regulates behavior through polycystin-dependent and -independent pathways.


CONCLUSIONS
Multiple ciliary transport pathways dependent on kinesin-II, OSM-3, and KLP-6 may act sequentially to build cilia and localize sensory ciliary membrane proteins such as the polycystins. We propose that KLP-6 and the polycystins function as an evolutionarily conserved ciliary unit. KLP-6 promises new routes to understanding cilia function, behavior, and ADPKD.
Peden
Erik M
EM
Molecular and Cellular Pharmacology, School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705, USA.
Barr
Maureen M
MM
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002874:Chromosome Mapping; D002923:Cilia / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D040461:Gene Components; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009475:Neurons, Afferent / Q000378:metabolism*; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012726:Sexual Behavior, Animal / Q000502:physiology*; D050396:TRPP Cation Channels
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D016547:Kinesins; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels; C500832:KLP-6 protein, C elegans