scholarly journals Cyclin Cln3p Links G1 Progression to Hyphal and Pseudohyphal Development in Candida albicans

2005 ◽  
Vol 4 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Catherine Bachewich ◽  
Malcolm Whiteway
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Critical Role ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Independent Manner ◽  
Cell Cycles ◽  
Environmental Controls ◽  
A Cell ◽  
Synthetically Lethal

ABSTRACT G1 cyclins coordinate environmental conditions with growth and differentiation in many organisms. In the pathogen Candida albicans, differentiation of hyphae is induced by environmental cues but in a cell cycle-independent manner. Intriguingly, repressing the G1 cyclin Cln3p under yeast growth conditions caused yeast cells to arrest in G1, increase in size, and then develop into hyphae and pseudohyphae, which subsequently resumed the cell cycle. Differentiation was dependent on Efg1p, Cph1p, and Ras1p, but absence of Ras1p was also synthetically lethal with repression of CLN3. In contrast, repressing CLN3 in environment-induced hyphae did not inhibit growth or the cell cycle, suggesting that yeast and hyphal cell cycles may be regulated differently. Therefore, absence of a G1 cyclin can activate developmental pathways in C. albicans and uncouple differentiation from the normal environmental controls. The data suggest that the G1 phase of the cell cycle may therefore play a critical role in regulating hyphal and pseudohyphal development in C. albicans.

scholarly journals A Forkhead Transcription Factor Is Important for True Hyphal as well as Yeast Morphogenesis in Candida albicans

2002 ◽  
Vol 1 (5) ◽  
pp. 787-798 ◽  
Author(s):  
Eric S. Bensen ◽  
Scott G. Filler ◽  
Judith Berman
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Cycle Progression ◽  
Forkhead Transcription Factors

ABSTRACT Candida albicans is an important pathogen of immunocompromised patients which grows with true hyphal, pseudohyphal, and yeast morphologies. The dynamics of cell cycle progression are markedly different in true hyphal relative to pseudohyphal and yeast cells, including nuclear movement and septin ring positioning. In Saccharomyces cerevisiae, two forkhead transcription factors (ScFKH1 and ScFKH2) regulate the expression of B-cyclin genes. In both S. cerevisiae and Schizosaccharomyces pombe, forkhead transcription factors also influence morphogenesis. To explore the molecular mechanisms that connect C. albicans morphogenesis with cell cycle progression, we analyzed CaFKH2, the single homolog of S. cerevisiae FKH1/FKH2. C. albicans cells lacking CaFkh2p formed constitutive pseudohyphae under all yeast and hyphal growth conditions tested. Under hyphal growth conditions levels of hyphae-specific mRNAs were reduced, and under yeast growth conditions levels of several genes encoding proteins likely to be important for cell wall separation were reduced. Together these results imply that Fkh2p is required for the morphogenesis of true hyphal as well as yeast cells. Efg1p and Cph1p, two transcription factors that contribute to C. albicans hyphal growth, were not required for the pseudohyphal morphology of fkh2 mutants, implying that Fkh2p acts in pathways downstream of and/or parallel to Efg1p and Cph1p. In addition, cells lacking Fkh2p were unable to damage human epithelial or endothelial cells in vitro, suggesting that Fkh2p contributes to C. albicans virulence.

scholarly journals Novel Response to Microtubule Perturbation in Meiosis

2005 ◽  
Vol 25 (11) ◽  
pp. 4767-4781 ◽  
Author(s):  
Andreas Hochwagen ◽  
Gunnar Wrobel ◽  
Marie Cartron ◽  
Philippe Demougin ◽  
Christa Niederhauser-Wiederkehr ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mitotic Cell ◽  
Yeast Cells ◽  
Microtubule Depolymerization ◽  
Cycle Progression ◽  
Cell Cycles ◽  
Cycle Arrest ◽  
A Cell ◽  
Surveillance Mechanism

ABSTRACT During the mitotic cell cycle, microtubule depolymerization leads to a cell cycle arrest in metaphase, due to activation of the spindle checkpoint. Here, we show that under microtubule-destabilizing conditions, such as low temperature or the presence of the spindle-depolymerizing drug benomyl, meiotic budding yeast cells arrest in G1 or G2, instead of metaphase. Cells arrest in G1 if microtubule perturbation occurs as they enter the meiotic cell cycle and in G2 if cells are already undergoing premeiotic S phase. Concomitantly, cells down-regulate genes required for cell cycle progression, meiotic differentiation, and spore formation in a highly coordinated manner. Decreased expression of these genes is likely to be responsible for halting both cell cycle progression and meiotic development. Our results point towards the existence of a novel surveillance mechanism of microtubule integrity that may be particularly important during specialized cell cycles when coordination of cell cycle progression with a developmental program is necessary.

scholarly journals Depletion of a Polo-like Kinase inCandida albicansActivates Cyclase-dependent Hyphal-like Growth

2003 ◽  
Vol 14 (5) ◽  
pp. 2163-2180 ◽  
Author(s):  
Catherine Bachewich ◽  
David Y. Thomas ◽  
Malcolm Whiteway
Keyword(s):  
Cell Cycle ◽  
Regulatory Networks ◽  
Hyphal Growth ◽  
Growth Conditions ◽  
Spindle Pole ◽  
Yeast Cells ◽  
Internal Cell ◽  
Spindle Pole Bodies ◽  
A Cell ◽  
Spindle Elongation

Morphogenesis in the fungal pathogen Candida albicans is an important virulence-determining factor, as a dimorphic switch between yeast and hyphal growth forms can increase pathogenesis. We identified CaCDC5, a cell cycle regulatory polo-like kinase (PLK) in C. albicans and demonstrate that shutting off its expression induced cell cycle defects and dramatic changes in morphology. Cells lacking CaCdc5p were blocked early in nuclear division with very short spindles and unseparated chromatin. GFP-tagged CaCdc5p localized to unseparated spindle pole bodies, the spindle, and chromatin, consistent with a role in spindle elongation at an earlier point in the cell cycle than that described for the homologue Cdc5p in yeast. Strikingly, the cell cycle defects were accompanied by the formation of hyphal-like filaments under yeast growth conditions. Filament growth was determinate, as the filaments started to die after 24 h. The filaments resembled serum-induced hyphae with respect to morphology, organization of cytoplasmic microtubules, localization of nuclei, and expression of hyphal-specific components. Filament formation required CaCDC35, but not EFG1 or CPH1. Similar defects in spindle elongation and a corresponding induction of filaments occurred when yeast cells were exposed to hydroxyurea. Because CaCdc5p does not appear to act as a direct repressor of hyphal growth, the data suggest that a target of CaCdc5p function is associated with hyphal-like development. Thus, an internal, cell cycle–related cue can activate hyphal regulatory networks in Candida.

Three proteins required for early steps in the protein secretory pathway also affect nuclear envelope structure and cell cycle progression in fission yeast

2002 ◽  
Vol 115 (2) ◽  
pp. 421-431
Author(s):  
Anna Matynia ◽  
Sandra S. Salus ◽  
Shelley Sazer
Keyword(s):  
Cell Cycle ◽  
Nuclear Envelope ◽  
Fission Yeast ◽  
Cell Cycle Progression ◽  
Secretory Pathway ◽  
Yeast Cells ◽  
Ran Gtpase ◽  
A Cell ◽  
Cell Cycle Block ◽  
Er Membrane

The Ran GTPase is an essential protein that has multiple functions in eukaryotic cells. Fission yeast cells in which Ran is misregulated arrest after mitosis with condensed, unreplicated chromosomes and abnormal nuclear envelopes. The fission yeast sns mutants arrest with a similar cell cycle block and interact genetically with the Ran system. sns-A10, sns-B2 and sns-B9 have mutations in the fission yeast homologues of S. cerevisiae Sar1p, Sec31p and Sec53p, respectively, which are required for the early steps of the protein secretory pathway. The three sns mutants accumulate a normally secreted protein in the endoplasmic reticulum (ER), have an increased amount of ER membrane, and the ER/nuclear envelope lumen is dilated. Neither a post-ER block in the secretory pathway, nor ER proliferation caused by overexpression of an integral ER membrane protein, results in a cell cycle-specific defect. Therefore, the arrest seen in sns-A10, sns-B2 and sns-B9 is most likely due to nuclear envelope defects that render the cells unable to re-establish the interphase organization of the nucleus after mitosis. As a consequence, these mutants are unable to decondense their chromosomes or to initiate of the next round of DNA replication.

scholarly journals A molecular marker for centriole maturation in the mammalian cell cycle.

1995 ◽  
Vol 130 (4) ◽  
pp. 919-927 ◽  
Author(s):  
B M Lange ◽  
K Gull
Keyword(s):  
Cell Cycle ◽  
Molecular Marker ◽  
Specific Cell ◽  
Cell Cycles ◽  
Functional Maturation ◽  
Ability To Act ◽  
Molecular Events ◽  
Mammalian Cell Cycle ◽  
A Cell ◽  
First Time

The centriole pair in animals shows duplication and structural maturation at specific cell cycle points. In G1, a cell has two centrioles. One of the centrioles is mature and was generated at least two cell cycles ago. The other centriole was produced in the previous cell cycle and is immature. Both centrioles then nucleate one procentriole each which subsequently elongate to full-length centrioles, usually in S or G2 phase. However, the point in the cell cycle at which maturation of the immature centriole occurs is open to question. Furthermore, the molecular events underlying this process are entirely unknown. Here, using monoclonal and polyclonal antibody approaches, we describe for the first time a molecular marker which localizes exclusively to one centriole of the centriolar pair and provides biochemical evidence that the two centrioles are different. Moreover, this 96-kD protein, which we name Cenexin (derived from the Latin, senex for "old man," and Cenexin for centriole) defines very precisely the mature centriole of a pair and is acquired by the immature centriole at the G2/M transition in prophase. Thus the acquisition of Cenexin marks the functional maturation of the centriole and may indicate a change in centriolar potential such as its ability to act as a basal body for axoneme development or as a congregating site for microtubule-organizing material.

scholarly journals TPR proteins required for anaphase progression mediate ubiquitination of mitotic B-type cyclins in yeast.

1996 ◽  
Vol 7 (5) ◽  
pp. 791-801 ◽  
Author(s):  
W Zachariae ◽  
K Nasmyth
Keyword(s):  
Cell Cycle ◽  
Cyclin B ◽  
Yeast Cells ◽  
Tetratricopeptide Repeat ◽  
Gene Products ◽  
Ubiquitin Pathway ◽  
Ubiquitin Protein Ligase ◽  
A Cell ◽  
Synthesis And Degradation

The abundance of B-type cyclin-CDK complexes is determined by regulated synthesis and degradation of cyclin subunits. Cyclin proteolysis is required for the final exit from mitosis and for the initiation of a new cell cycle. In extracts from frog or clam eggs, degradation is accompanied by ubiquitination of cyclin. Three genes, CDC16, CDC23, and CSE1 have recently been shown to be required specifically for cyclin B proteolysis in yeast. To test whether these genes are required for cyclin ubiquitination, we prepared extracts from G1-arrested yeast cells capable of conjugating ubiquitin to the B-type cyclin Clb2. The ubiquitination activity was cell cycle regulated, required Clb2's destruction box, and was low if not absent in cdc16, cdc23, cdc27, and cse1 mutants. Furthermore all these mutants were also defective in ubiquitination of another mitotic B-type cyclin, Clb3. The Cdc16, Cdc23, and Cdc27 proteins all contain several copies of the tetratricopeptide repeat and are subunits of a complex that is required for the onset of anaphase. The finding that gene products that are required for ubiquitination of Clb2 and Clb3 are also required for cyclin proteolysis in vivo provides the best evidence so far that cyclin B is degraded via the ubiquitin pathway in living cells. Xenopus homologues of Cdc16 and Cdc27 have meanwhile been shown to be associated with a 20S particle that appears to function as a cell cycle-regulated ubiquitin-protein ligase.

scholarly journals The evaluation of proliferation ability of cardiomyocytes in heart failure

2021 ◽  
Vol 271 ◽  
pp. 03064
Author(s):  
Mengzi Gao
Keyword(s):  
Heart Failure ◽  
Cell Cycle ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Rna Seq ◽  
Cell Cycles ◽  
A Cell ◽  
Proliferation Ability ◽  
Heat Failure

The proliferation ability of cardiomyocytes is always under a controversial situation, especially under some stress condition such as heart failure disease and external damages. Heat failure (HF) is a complex clinical syndrome that results from left ventricular myocardial dysfunction and contributes to dyspnea, fatigue and fluid retention. The proliferation ability is related to the cell cycles and lot of cell-cycle related genes are involved in the evaluation of proliferation ability of cardiomyocytes. RNA-seq is a quite common technique in evaluate the transcription expression pattern of genes in many studies. Here in our article we analyzed the existing RNA-seq dataset to evaluate the mRNA expression level of several genes which can be indicators of the activity of cell cycles. We found that the cyclin D2 which is a cell cycle activator is upregulated in dilated cardiomyopathy (DCM) disease, indicating that the proliferation ability may be higher in DCM heart. The results throw light on the proliferation research of adult cardiomyocytes.

scholarly journals Energy Starvation Induces a Cell Cycle Arrest in Escherichia coli by Triggering Degradation of the DnaA Initiator Protein

2021 ◽  
Vol 8 ◽  
Author(s):  
Godefroid Charbon ◽  
Belén Mendoza-Chamizo ◽  
Christopher Campion ◽  
Xiaobo Li ◽  
Peter Ruhdal Jensen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Growth Conditions ◽  
Chromosome Replication ◽  
Replication Initiation ◽  
Atp Depletion ◽  
Initiator Protein ◽  
Cycle Arrest ◽  
A Cell

During steady-state Escherichia coli growth, the amount and activity of the initiator protein, DnaA, controls chromosome replication tightly so that initiation only takes place once per origin in each cell cycle, regardless of growth conditions. However, little is known about the mechanisms involved during transitions from one environmental condition to another or during starvation stress. ATP depletion is one of the consequences of long-term carbon starvation. Here we show that DnaA is degraded in ATP-depleted cells. A chromosome replication initiation block is apparent in such cells as no new rounds of DNA replication are initiated while replication events that have already started proceed to completion.

scholarly journals The oscillation of mitotic kinase governs cell cycle latches

2021 ◽  
Author(s):  
Bela Novak ◽  
John J Tyson
Keyword(s):  
Cell Cycle ◽  
Negative Feedback ◽  
Molecular Switches ◽  
Feedback Loops ◽  
Yeast Cells ◽  
Cyclin Dependent Kinases ◽  
Mitotic Kinase ◽  
Daughter Cells ◽  
Negative Feedback Loops ◽  
A Cell

SummaryIn order to transmit a eukaryotic cell’s genome accurately from mother cell to daughter cells, it is essential that the basic events of the cell division cycle (DNA synthesis and mitosis) occur once and only once per cycle, i.e., that a cell progresses irreversibly from G1 to S to G2 to M and back to G1. Irreversible progression through the cell cycle is assured by a sequence of ‘latching’ molecular switches, based on molecular interactions among cyclin-dependent kinases and their auxiliary partners. Positive feedback loops (++ or −−) create bistable switches with latching properties, and negative feedback loops drive progression from one stage to the next. In budding yeast (Saccharomyces cerevisiae) these events are coordinated by double-negative feedback loops between Clb-dependent kinases (Clb1-6) and their antagonists (APC:Cdh1 and Sic1). If the coordinating signal is compromised, either by deletion of Clb1-5 proteins or expression of non-degradable Clb2, then irreversibility is lost and yeast cells exhibit multiple rounds of DNA replication or mitotic exit events (Cdc14 endocycles). Using mathematical modelling of a stripped-down control network, we show how endocycles arise because the switches fail to latch, and the gates swing back and forth by the action of the negative feedback loops.

scholarly journals Cell size distribution of lineage data: analytic results and parameter inference

2020 ◽  
Author(s):  
Chen Jia ◽  
Abhyudai Singh ◽  
Ramon Grima
Keyword(s):  
Size Distribution ◽  
Cell Size ◽  
Cell Tracking ◽  
Cell Lineage ◽  
Growth Conditions ◽  
Cell Size Distribution ◽  
Time Resolved ◽  
Cell Cycles ◽  
A Cell ◽  
Non Gaussian

AbstractRecent advances in single-cell technologies have enabled time-resolved measurements of the cell size over several cell cycles. This data encodes information on how cells correct size aberrations so that they do not grow abnormally large or small. Here we formulate a piecewise deterministic Markov model describing the evolution of the cell size over many generations, for all three cell size homeostasis strategies (timer, sizer, and adder). The model is solved to obtain an analytical expression for the non-Gaussian cell size distribution in a cell lineage; the theory is used to understand how the shape of the distribution is influenced by the parameters controlling the dynamics of the cell cycle and by the choice of cell tracking protocol. The theoretical cell size distribution is found to provide an excellent match to the experimental cell size distribution of E. coli lineage data collected under various growth conditions.

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