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Title: The roles of ciliary kinesins, and the functions of intraflagellar transport proteins
Author: Pooranachandran, Niedharsan
ISNI:       0000 0004 5991 7315
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Microtubule-dependent motors, kinesins, drive transport of proteins in the ciliary shaft. 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 almost 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 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 these 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. In addition to this, double mutants of different combinations of kinesins were generated: klp-6, kif17, kif3b, kif3cl. However, the double mutants did not display any obvious defects. 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.
Supervisor: Malicki, Jarema Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available