title: Unexpected Roles for Ciliary Kinesins and Intraflagellar Transport Proteins.
abstract: Transport of proteins in the ciliary shaft is driven by microtubule-dependent motors, kinesins. Prior studies suggested that the heterotrimeric ciliary kinesin may be dispensable for certain aspects of transport in specialized cilia of vertebrate photoreceptor cells. To test this possibility further, we analyzed the mutant phenotype of the zebrafish kif3a gene, which encodes the common motor subunit of heterotrimeric ciliary kinesins. Cilia are absent in all organs examined, leading to the conclusion that kif3a is indispensable for ciliogenesis in all cells, including photoreceptors. Unexpectedly, kif3a function precedes ciliogenesis as ciliary basal bodies are mispositioned in mutant photoreceptors. This phenotype is much less pronounced in intraflagellar transport (IFT) mutants and reveals that kif3a has a much broader role than previously assumed. Despite the severity of their basal body phenotype, kif3a mutant photoreceptors survive longer compared to those in IFT mutants, which display much weaker basal body mispositioning. This effect is absent in kif3a;IFT double mutants, indicating that IFT proteins have ciliary transport-independent roles, which add to the severity of their photoreceptor phenotype. kif3a is dispensable for basal body docking in otic vesicle sensory epithelia and, surprisingly, short cilia form in mechanosensory cristae even in the absence of kif3a In contrast to Kif3a, the functions of the Kif3c-related protein, encoded by the kif3c-like (kif3cl) gene, and the homodimeric ciliary kinesin, kif17, are dispensable for photoreceptor morphogenesis. These studies demonstrate unexpected new roles for both ciliary heterotrimeric kinesins and IFT particle genes and clarify the function of kif17, the homodimeric ciliary kinesin gene.
authors.affiliation: Bateson Centre and the Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom.
authors.forename: Niedharsan
authors.initials: N
authors.lastname: Pooranachandran
authors.affiliation: Bateson Centre and the Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom j.malicki@sheffield.ac.uk.
authors.forename: Jarema J
authors.initials: JJ
authors.lastname: Malicki
mesh_terms: D000818:Animals; D064652:Basal Bodies / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D005407:Flagella / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D021381:Protein Transport; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D016547:Kinesins
keywords: basal body; cilia; intraflagellar transport; kinesin; sensory neuron