Candida albicans SH3-domain proteins involved in hyphal growth, cytokinesis, and vacuolar morphology

Reijnst, Patrick; Jorde, Sigyn; Wendland, Jürgen

doi:10.1007/s00294-010-0301-7

Cited by 19 publications

(16 citation statements)

References 40 publications

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“…Our data suggest that Cyk3 and the interaction of the Inn1 C2-domain with Chs2 represent alternative targets for the development of novel small molecule inhibitors of cytokinesis in pathogenic yeasts. In support of this idea, the orthologues of ScChs2 and Cyk3 have been shown to be essential in Candida albicans (Mio et al, 1996; Inn1 regulates Chs2 during cytokinesis 5463 Munro et al, 2001;Reijnst et al, 2010), although the orthologue of Inn1 has yet to be characterised. Moreover, the orthologue of Inn1 in Cryptococcus neoformans is important for cell division at 37˚C, and even a hypomorphic allele blocks virulence in a mouse model of yeast infection (Fox et al, 2003).…”

Section: Discussionmentioning

confidence: 82%

Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts

Devrekanli

Foltman

Roncero

et al. 2012

Journal of Cell Science

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SummaryThe chitin synthase that makes the primary septum during cell division in budding yeasts is an important therapeutic target with an unknown activation mechanism. We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis. By combining a novel degron allele of INN1 with a point mutation in the C2-domain, we screened for mutations in other genes that suppress the resulting defect in cell division. In this way, we identified 22 dominant mutations of CHS2 (chitin synthase II) that map to two neighbouring sites in the catalytic domain. Chs2 in isolated cell membranes is normally nearly inactive (unless protease treatment is used to bypass inhibition); however, the dominant suppressor allele Chs2-V377I has enhanced activity in vitro. We show that Inn1 associates with Chs2 in yeast cell extracts. It also interacts in a yeast two-hybrid assay with the N-terminal 65% of Chs2, which contains the catalytic domain. In addition to compensating for mutations in the Inn1 C2-domain, the dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the Cyk3 protein.Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis. These findings suggest novel approaches for developing future drugs against important fungal pathogens.

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Section: Discussionmentioning

confidence: 82%

Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts

Devrekanli

Foltman

Roncero

et al. 2012

Journal of Cell Science

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“…The higher than normal prevalence of depressive disorders in individuals who suffer from chronic inflammatory diseases indirectly supports such an association [4]. Patients who are treated with interleukin (IL)-2 or interferon-α for cancer and infectious diseases develop neurovegetative and somatic symptoms, and about 30–45% also have depressed mood, anxiety and/or cognitive impairment [4,5,6]. These symptoms are related to the immunotherapy and are ameliorated by antidepressant treatment [7].…”

Section: Introductionmentioning

confidence: 99%

Depressive Symptoms and Proinflammatory Cytokine Levels in Chronic Renal Failure Patients

Dervişoğlu¹,

Kır²,

Kalender³

et al. 2008

Nephron Clin Pract

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Background/Aims: Cytokine secretion is known to play an important role in the pathophysiology of depression, and levels of proinflammatory cytokines are increased in chronic renal failure (CRF) patients. The objective of this study was to examine the correlation between levels of proinflammatory cytokines in CRF patients and degree of depression. Methods: 31 patients on hemodialysis, 31 patients on continuous ambulatory peritoneal dialysis, and 31 conservatively managed chronic kidney disease (CKD) patients were enrolled in this study. Depressive symptoms were measured with the Beck Depression Inventory (BDI), and ‘elevated symptoms of depression’ were defined as a BDI score ≧17. IL-6 and TNFα cytokine levels were measured by ELISA. Results: ‘Elevated symptoms of depression’ occurred in 37 of 93 patients (40%). IL-6 and TNFα levels were not significantly different among CRF patients with and without elevated depressive symptoms (p = 0.937 and p = 0.414, respectively). When analyzed by treatment subgroup, proinflammatory cytokine levels were not significantly different in patients with and without elevated symptoms of depression. Conclusion: In patients with CRF, elevated symptoms of depression were not associated with increased cytokine levels.

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“…Characteristically, during hyphal growth large vacuoles are formed in the germ cell and in the rear parts of the hyphal filaments. An unequal distribution of vacuoles was also shown to influence the timing of branch emergence (Veses et al, 2008); however, fragmented vacuoles, per se, do not abolish polarized morphogenesis, which was recently also shown in a Caboi2 mutant (Reijnst et al, 2010).…”

Section: Introductionmentioning

confidence: 73%

Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5

et al. 2010

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Recently, a link between endocytosis and hyphal morphogenesis has been identified in Candida albicans via the Wiskott-Aldrich syndrome gene homologue WAL1. To get a more detailed mechanistic understanding of this link we have investigated a potentially conserved interaction between Wal1 and the C. albicans WASP-interacting protein (WIP) homologue encoded by VRP1. Deletion of both alleles of VRP1 results in strong hyphal growth defects under serum inducing conditions but filamentation can be observed on Spider medium. Mutant vrp1 cells show a delay in endocytosis -measured as the uptake and delivery of the lipophilic dye FM4-64 into small endocytic vesicles -compared to the wild-type. Vacuolar morphology was found to be fragmented in a subset of cells and the cortical actin cytoskeleton was depolarized in vrp1 daughter cells. The morphology of the vrp1 null mutant could be complemented by reintegration of the wild-type VRP1 gene at the BUD3 locus. Using the yeast two-hybrid system we could demonstrate an interaction between the C-terminal part of Vrp1 and the N-terminal part of Wal1, which contains the WH1 domain. Furthermore, we found that Myo5 has several potential interaction sites on Vrp1. This suggests that a Wal1-Vrp1-Myo5 complex plays an important role in endocytosis and the polarized localization of the cortical actin cytoskeleton to promote polarized hyphal growth in C. albicans.

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Candida albicans SH3-domain proteins involved in hyphal growth, cytokinesis, and vacuolar morphology

Cited by 19 publications

References 40 publications

Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts

Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts

Depressive Symptoms and Proinflammatory Cytokine Levels in Chronic Renal Failure Patients

Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5

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