Candida albicans Kinesin Kar3 Depends on a Cik1-Like Regulatory Partner Protein for Its Roles in Mating, Cell Morphogenesis, and Bipolar Spindle Formation

Author:

Frazer Corey1,Joshi Monika1,Delorme Caroline1,Davis Darlene1,Bennett Richard J.2,Allingham John S.1

Affiliation:

1. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada

2. Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, USA

Abstract

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 Ca Kar3 is required for transition between these morphological states, as well as for mitotic progression and karyogamy. While kinesin-14 proteins are ubiquitous, Ca Kar3 homologs in hemiascomycete fungi are unique because they form heterodimers with noncatalytic kinesin-like proteins. Thus, Ca Kar3-based motors may represent a novel antifungal drug target. We have identified and examined the roles of a kinesin-like regulator of Ca Kar3. We show that orf19.306 (dubbed CaCIK1 ) encodes a protein that forms a heterodimer with Ca Kar3, localizes Ca Kar3 to spindle pole bodies, and can bind microtubules and influence Ca Kar3 mechanochemistry despite lacking an ATPase activity of its own. Similar to Ca Kar3 depletion, loss of Ca Cik1 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.

Publisher

American Society for Microbiology

Subject

Molecular Biology,General Medicine,Microbiology

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