title: Candida albicans Kinesin Kar3 Depends on a Cik1-Like Regulatory Partner Protein for Its Roles in Mating, Cell Morphogenesis, and Bipolar Spindle Formation.
abstract: Candida albicans is a major fungal pathogen whose virulence is associated with its ability to transition from a budding yeast form to invasive hyphal filaments. The kinesin-14 family member CaKar3 is required for transition between these morphological states, as well as for mitotic progression and karyogamy. While kinesin-14 proteins are ubiquitous, CaKar3 homologs in hemiascomycete fungi are unique because they form heterodimers with noncatalytic kinesin-like proteins. Thus, CaKar3-based motors may represent a novel antifungal drug target. We have identified and examined the roles of a kinesin-like regulator of CaKar3. We show that orf19.306 (dubbed CaCIK1) encodes a protein that forms a heterodimer with CaKar3, localizes CaKar3 to spindle pole bodies, and can bind microtubules and influence CaKar3 mechanochemistry despite lacking an ATPase activity of its own. Similar to CaKar3 depletion, loss of CaCik1 results in cell cycle arrest, filamentation defects, and an inability to undergo karyogamy. Furthermore, an examination of the spindle structure in cells lacking either of these proteins shows that a large proportion have a monopolar spindle or two dissociated half-spindles, a phenotype unique to the C. albicans kinesin-14 homolog. These findings provide new insights into mitotic spindle structure and kinesin motor function in C. albicans and identify a potentially vulnerable target for antifungal drug development.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Corey
authors.initials: C
authors.lastname: Frazer
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Joshi
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Delorme
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Darlene
authors.initials: D
authors.lastname: Davis
authors.affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bennett
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada allinghj@queensu.ca.
authors.forename: John S
authors.initials: JS
authors.lastname: Allingham
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000935:Antifungal Agents / Q000378:metabolism; D002176:Candida albicans / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D018844:Cyclin-Dependent Kinases; D000251:Adenosine Triphosphatases; D016547:Kinesins