Candida albicans Kinesin Kar3 Depends on a Cik1-Like Regulatory Partner Protein for Its Roles in Mating, Cell Morphogenesis, and Bipolar Spindle Formation
Candida albicans Kinesin Kar3 Depends on a Cik1-Like Regulatory Partner Protein for Its Roles in Mating, Cell Morphogenesis, and Bipolar Spindle Formation
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DOI：
10.1128/ec.00015-15
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发表时间：
2015-08-01
期刊：
影响因子：
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通讯作者：
Allingham, John S.
中科院分区：
文献类型：
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作者：
Frazer, Corey;Joshi, Monika;Allingham, John S.
白色念珠菌是一种主要的真菌病原体，其毒力与其从芽殖酵母形式转变为侵入性菌丝丝的能力有关。驱动蛋白-14家族成员CaKar 3是这些形态状态之间的过渡所必需的，也是有丝分裂进程和核配体所必需的。虽然驱动蛋白-14蛋白是普遍存在的，但半子囊真菌中的CaKar 3同系物是独特的，因为它们与非催化驱动蛋白样蛋白形成异二聚体。因此，基于CaKar 3的马达可能代表一种新的抗真菌药物靶标。我们已经确定并研究了CaKar 3的驱动蛋白样调节剂的作用。我们发现orf19.306（称为CaCIK 1）编码的蛋白质与CaKar 3形成异源二聚体，将CaKar 3定位于纺锤体极体，并且可以结合微管并影响CaKar 3机械化学，尽管缺乏其自身的ATP酶活性。与CaKar 3耗竭类似，CaCik 1的缺失导致细胞周期停滞、表达缺陷和不能进行核融合。此外，在缺乏这些蛋白质的细胞中对纺锤体结构的检查表明，大部分细胞具有单极纺锤体或两个分离的半纺锤体，这是C.白色念珠菌驱动蛋白-14同源物这些发现为深入了解C.白色念珠菌，并确定抗真菌药物开发的潜在脆弱目标。
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.