Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal

ABSTRACT Mitotic spindles assume a bipolar architecture through the concerted actions of microtubules, motors, and cross-linking proteins. In most eukaryotes, kinesin-5 motors are essential to this process, and cells will fail to form a bipolar spindle without kinesin-5 activity. Remarkably, inactiv...

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Autores principales:	Irsa Shoukat, Corey Frazer, John S. Allingham
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Candida albicans yeast kinesin microtubule dynamics mitotic spindle Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/63c801dff41e4ee58f57052cc447ac8a
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spelling	oai:doaj.org-article:63c801dff41e4ee58f57052cc447ac8a2021-11-15T15:22:24ZKinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal10.1128/mSphere.00610-192379-5042https://doaj.org/article/63c801dff41e4ee58f57052cc447ac8a2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00610-19https://doaj.org/toc/2379-5042ABSTRACT Mitotic spindles assume a bipolar architecture through the concerted actions of microtubules, motors, and cross-linking proteins. In most eukaryotes, kinesin-5 motors are essential to this process, and cells will fail to form a bipolar spindle without kinesin-5 activity. Remarkably, inactivation of kinesin-14 motors can rescue this kinesin-5 deficiency by reestablishing the balance of antagonistic forces needed to drive spindle pole separation and spindle assembly. We show that the yeast form of the opportunistic fungus Candida albicans assembles bipolar spindles in the absence of its sole kinesin-5, CaKip1, even though this motor exhibits stereotypical cell-cycle-dependent localization patterns within the mitotic spindle. However, cells lacking CaKip1 function have shorter metaphase spindles and longer and more numerous astral microtubules. They also show defective hyphal development. Interestingly, a small population of CaKip1-deficient spindles break apart and reform two bipolar spindles in a single nucleus. These spindles then separate, dividing the nucleus, and then elongate simultaneously in the mother and bud or across the bud neck, resulting in multinucleate cells. These data suggest that kinesin-5-independent mechanisms drive assembly and elongation of the mitotic spindle in C. albicans and that CaKip1 is important for bipolar spindle integrity. We also found that simultaneous loss of kinesin-5 and kinesin-14 (CaKar3Cik1) activity is lethal. This implies a divergence from the antagonistic force paradigm that has been ascribed to these motors, which could be linked to the high mitotic error rate that C. albicans experiences and often exploits as a generator of diversity. IMPORTANCE Candida albicans is one of the most prevalent fungal pathogens of humans and can infect a broad range of niches within its host. This organism frequently acquires resistance to antifungal agents through rapid generation of genetic diversity, with aneuploidy serving as a particularly important adaptive mechanism. This paper describes an investigation of the sole kinesin-5 in C. albicans, which is a major regulator of chromosome segregation. Contrary to other eukaryotes studied thus far, C. albicans does not require kinesin-5 function for bipolar spindle assembly or spindle elongation. Rather, this motor protein associates with the spindle throughout mitosis to maintain spindle integrity. Furthermore, kinesin-5 loss is synthetically lethal with loss of kinesin-14—canonically an opposing force producer to kinesin-5 in spindle assembly and anaphase. These results suggest a significant evolutionary rewiring of microtubule motor functions in the C. albicans mitotic spindle, which may have implications in the genetic instability of this pathogen.Irsa ShoukatCorey FrazerJohn S. AllinghamAmerican Society for MicrobiologyarticleCandida albicansyeastkinesinmicrotubule dynamicsmitotic spindleMicrobiologyQR1-502ENmSphere, Vol 4, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans yeast kinesin microtubule dynamics mitotic spindle Microbiology QR1-502
spellingShingle	Candida albicans yeast kinesin microtubule dynamics mitotic spindle Microbiology QR1-502 Irsa Shoukat Corey Frazer John S. Allingham Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal
description	ABSTRACT Mitotic spindles assume a bipolar architecture through the concerted actions of microtubules, motors, and cross-linking proteins. In most eukaryotes, kinesin-5 motors are essential to this process, and cells will fail to form a bipolar spindle without kinesin-5 activity. Remarkably, inactivation of kinesin-14 motors can rescue this kinesin-5 deficiency by reestablishing the balance of antagonistic forces needed to drive spindle pole separation and spindle assembly. We show that the yeast form of the opportunistic fungus Candida albicans assembles bipolar spindles in the absence of its sole kinesin-5, CaKip1, even though this motor exhibits stereotypical cell-cycle-dependent localization patterns within the mitotic spindle. However, cells lacking CaKip1 function have shorter metaphase spindles and longer and more numerous astral microtubules. They also show defective hyphal development. Interestingly, a small population of CaKip1-deficient spindles break apart and reform two bipolar spindles in a single nucleus. These spindles then separate, dividing the nucleus, and then elongate simultaneously in the mother and bud or across the bud neck, resulting in multinucleate cells. These data suggest that kinesin-5-independent mechanisms drive assembly and elongation of the mitotic spindle in C. albicans and that CaKip1 is important for bipolar spindle integrity. We also found that simultaneous loss of kinesin-5 and kinesin-14 (CaKar3Cik1) activity is lethal. This implies a divergence from the antagonistic force paradigm that has been ascribed to these motors, which could be linked to the high mitotic error rate that C. albicans experiences and often exploits as a generator of diversity. IMPORTANCE Candida albicans is one of the most prevalent fungal pathogens of humans and can infect a broad range of niches within its host. This organism frequently acquires resistance to antifungal agents through rapid generation of genetic diversity, with aneuploidy serving as a particularly important adaptive mechanism. This paper describes an investigation of the sole kinesin-5 in C. albicans, which is a major regulator of chromosome segregation. Contrary to other eukaryotes studied thus far, C. albicans does not require kinesin-5 function for bipolar spindle assembly or spindle elongation. Rather, this motor protein associates with the spindle throughout mitosis to maintain spindle integrity. Furthermore, kinesin-5 loss is synthetically lethal with loss of kinesin-14—canonically an opposing force producer to kinesin-5 in spindle assembly and anaphase. These results suggest a significant evolutionary rewiring of microtubule motor functions in the C. albicans mitotic spindle, which may have implications in the genetic instability of this pathogen.
format	article
author	Irsa Shoukat Corey Frazer John S. Allingham
author_facet	Irsa Shoukat Corey Frazer John S. Allingham
author_sort	Irsa Shoukat
title	Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal
title_short	Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal
title_full	Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal
title_fullStr	Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal
title_full_unstemmed	Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal
title_sort	kinesin-5 is dispensable for bipolar spindle formation and elongation in <named-content content-type="genus-species">candida albicans</named-content>, but simultaneous loss of kinesin-14 activity is lethal
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/63c801dff41e4ee58f57052cc447ac8a
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Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in <named-content content-type="genus-species">Candida albicans</named-content>, but Simultaneous Loss of Kinesin-14 Activity Is Lethal

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