Dynein-dependent nuclear dynamics affect morphogenesis in <i>Candida albicans</i> by means of the Bub2p spindle checkpoint

Finley, Kenneth R.; Bouchonville, Kelly J.; Quick, Aaron; Berman, Judith

doi:10.1242/jcs.03498

Cited by 15 publications

(23 citation statements)

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“…Mutants lacking either protein produced shorter mating projections than wild-type strains, but in both cases, nuclei were able to migrate to the tip of the mating projection. This result contrasts sharply with nuclear positioning in hyphal cells of C. albicans, where the absence of Dyn1p was found to often block nuclear migration into the growing hyphal cell (18,37). The lack of nuclear migration in dyn1 mutants prevented efficient growth of hyphal cells and resulted in a marked defect in filamentation.…”

Section: Discussionmentioning

confidence: 68%

“…6B). This is in contrast to ⌬dyn1/ ⌬dyn1 mutants, where nuclear division often takes place within the mother cell of yeast cells, although the daughter nucleus can subsequently segregate to the daughter bud prior to septum formation (18,37).…”

Section: Vol 7 2008 Role Of C Albicans Kar3p In Mitosis 1467mentioning

confidence: 73%

“…The Kar3-GFP-labeled strain also coexpressed a tubulin 2-RFP (Tub2-RFP) fusion protein to compare the localization of these proteins in wild-type cells. The Tub2-RFP fusion protein labels the ␤ subunit of tubulin and has previously been used to accurately monitor microtubules, mitotic spindles, and spindle pole bodies in C. albicans (17,18,23). (Fig.…”

Section: Vol 7 2008 Role Of C Albicans Kar3p In Mitosis 1467mentioning

confidence: 99%

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Microtubule Motor Protein Kar3 Is Required for Normal Mitotic Division and Morphogenesis in Candida albicans

Sherwood

Bennett

2008

Eukaryot Cell

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The kinesin-related protein Kar3 is a minus end-directed molecular motor that plays a multifunctional role in microtubule-directed nuclear movement. Previously, it was shown that Candida albicans Kar3p is critical for nuclear fusion during mating as kar3 mutants were defective in karyogamy. In this study, we confirm that Kar3p is required for nuclear congression in mating but that neither Kar3p nor the dynein motor protein Dyn1p is required for nuclear migration in the mating projection prior to cell fusion. In addition, we show that C. albicans Kar3p plays an important role in the cell and colony morphology of mitotically dividing cells, as evidenced by diminished filamentation of kar3 cells on Spider medium and an increased tendency of mutant cells to form pseudohyphal cells in liquid culture. Loss of Kar3p also led to defects in nuclear division, causing cells to grow slowly and exhibit reduced viability compared to wild-type cells. Slow growth was due, at least in part, to delayed cell cycle progression, as cells lacking Kar3p accumulated in anaphase of the cell cycle. Consistent with a role in mitotic division, Kar3 protein was shown to localize to the spindle pole bodies. Finally, kar3 cells exhibited unstable or aberrant mitotic spindles, a finding that accounts for the delay in cell cycle progression and decreased viability of these cells. We suggest that the altered morphology of kar3 cells is a direct consequence of the delay in anaphase, and this leads to increased polarized growth and pseudohypha formation.

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Section: Discussionmentioning

confidence: 68%

Section: Vol 7 2008 Role Of C Albicans Kar3p In Mitosis 1467mentioning

confidence: 73%

Section: Vol 7 2008 Role Of C Albicans Kar3p In Mitosis 1467mentioning

confidence: 99%

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Microtubule Motor Protein Kar3 Is Required for Normal Mitotic Division and Morphogenesis in Candida albicans

Sherwood

Bennett

2008

Eukaryot Cell

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“…Our results suggest that C. orbiculare has plant pathogen-specific roles for the two-component GAP and its GTPase that are involved in functional development in various yeast and fungal species (Figure 10). In S. cerevisiae and C. albicans, Bub2p/Bfa1p negatively regulates GTPase Tem1p, thereby triggering the MEN pathway, which controls mitotic exit and cytokinesis via Ser/Thr kinase Cdc15p (Bardin and Amon, 2001;Finley et al, 2008;Milne et al, 2014). A similar cascade, the SIN, has been reported in S. pombe and A. nidulans, and its primary role appears to be in regulating septation rather than mitotic exit (Bruno et al, 2001;Krapp and Simanis, 2008;Kim et al, 2009).…”

Section: Global Regulation Of Two-component Gap and Gtpase Among Yeasmentioning

confidence: 68%

Colletotrichum orbiculare Regulates Cell Cycle G1/S Progression via a Two-Component GAP and a GTPase to Establish Plant Infection

Fukada

Kubo

2015

Plant Cell

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“…The ability to switch among these morphologies is required for C. albicans pathogenicity (38,39), suggesting that multiple morphologies contribute to host infection. Filamentous growth can be triggered by various stimuli, including oxidative stress (40), activation of the DNA damage, and replication checkpoints due to exogenous or endogenous DNA damage (41,42), or by cell-cycle delays resulting from perturbed microtubule dynamics or spindle checkpoint activation (43,44; reviewed in ref. 45).…”

Section: Resultsmentioning

confidence: 99%

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

Rosa

Boyartchuk

Zhu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

127

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Candida albicans is a ubiquitous opportunistic pathogen that is the most prevalent cause of hospital-acquired fungal infections. In mammalian hosts, C. albicans is engulfed by phagocytes that attack the pathogen with DNA-damaging reactive oxygen species (ROS). Acetylation of histone H3 lysine 56 (H3K56) by the fungal-specific histone acetyltransferase Rtt109 is important for yeast model organisms to survive DNA damage and maintain genome integrity. To assess the importance of Rtt109 for C. albicans pathogenicity, we deleted the predicted homolog of Rtt109 in the clinical C. albicans isolate, SC5314. C. albicans rtt109 −/− mutant cells lack acetylated H3K56 (H3K56ac) and are hypersensitive to genotoxic agents. Additionally, rtt109 −/− mutant cells constitutively display increased H2A S129 phosphorylation and elevated DNA repair gene expression, consistent with endogenous DNA damage. Importantly, C. albicans rtt109 −/− cells are significantly less pathogenic in mice and more susceptible to killing by macrophages in vitro than are wild-type cells. Via pharmacological inhibition of the host NADPH oxidase enzyme, we show that the increased sensitivity of rtt109 −/− cells to macrophages depends on the host's ability to generate ROS, providing a mechanistic link between the drug sensitivity, gene expression, and pathogenesis phenotypes. We conclude that Rtt109 is particularly important for fungal pathogenicity, suggesting a unique target for therapeutic antifungal compounds.acetylation | chromatin | fungal pathogenesis | DNA damage resistance | macrophage

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Dynein-dependent nuclear dynamics affect morphogenesis in Candida albicans by means of the Bub2p spindle checkpoint

Cited by 15 publications

References 0 publications

Microtubule Motor Protein Kar3 Is Required for Normal Mitotic Division and Morphogenesis in Candida albicans

Microtubule Motor Protein Kar3 Is Required for Normal Mitotic Division and Morphogenesis in Candida albicans

Colletotrichum orbiculare Regulates Cell Cycle G1/S Progression via a Two-Component GAP and a GTPase to Establish Plant Infection

Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis

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