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Is Aggregate-Dependent Yeast Aging Fortuitous? A Model of Damage Segregation and Aggregate Dynamics.

ABSTRACT: During cytokinesis in Saccharomyces cerevisiae, damaged proteins are distributed unequally between the daughter and mother cells. The retention of these proteins is correlated with yeast aging. Even though evidence suggests that aggregates are retained due to an underlying molecular mechanism, the debate on whether an active mechanism is necessary for this asymmetry remains unsolved. In particular, passive diffusion and a bud-specific dilution remain as possible explanations. Here, a computational and mathematical model is provided to test whether passive mechanisms alone are sufficient to account for the aggregate distribution patterns and the aggregate kinetics observed in living cells. To this author's knowledge, this is the most comprehensive model available on this subject and the only one combining key potentially essential passive-only mechanisms proposed in existing bibliography-namely, the geometrical effect of the dividing yeast cell on the diffusion of protein aggregates, and the possibility of aggregate binding and aggregate formation at different rates. Results suggest that although passive processes alone can reproduce certain averaged observables from experimental bibliography, they are insufficient to vindicate aggregate activity observed in living budding yeast cells. These results are complemented by showing that under basic forms of active quality control, discrepancies between the outputs of the model and experimental bibliography are reduced.

SUBMITTER: Andrade-Restrepo M

PROVIDER: S-EPMC5768517 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Is Aggregate-Dependent Yeast Aging Fortuitous? A Model of Damage Segregation and Aggregate Dynamics.

Andrade-Restrepo Martín M

Biophysical journal 20171201 11

During cytokinesis in Saccharomyces cerevisiae, damaged proteins are distributed unequally between the daughter and mother cells. The retention of these proteins is correlated with yeast aging. Even though evidence suggests that aggregates are retained due to an underlying molecular mechanism, the debate on whether an active mechanism is necessary for this asymmetry remains unsolved. In particular, passive diffusion and a bud-specific dilution remain as possible explanations. Here, a computation ...[more]

PMID: 29212000

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Project description:Many fungal species, including pathogens, undergo a morphogenetic response called filamentous growth, where cells differentiate into a specialized cell type to promote nutrient foraging and surface colonization. Despite the fact that filamentous growth is required for virulence in some plant and animal pathogens, certain aspects of this behavior remain poorly understood. By examining filamentous growth in the budding yeast Saccharomyces cerevisiae and the opportunistic pathogen Candida albicans, we identify responses where cells undergo filamentous growth in groups of cells or aggregates. In S. cerevisiae, aggregate invasive growth was regulated by signaling pathways that control normal filamentous growth. These pathways promoted aggregation in part by fostering aspects of microbial cooperation. For example, aggregate invasive growth required cellular contacts mediated by the flocculin Flo11p, which was produced at higher levels in aggregates than cells undergoing regular invasive growth. Aggregate invasive growth was also stimulated by secreted enzymes, like invertase, which produce metabolites that are shared among cells. Aggregate invasive growth was also induced by alcohols that promote density-dependent filamentous growth in yeast. Aggregate invasive growth also required highly polarized cell morphologies, which may affect the packing or organization of cells. A directed selection experiment for aggregating phenotypes uncovered roles for the fMAPK and RAS pathways, which indicates that these pathways play a general role in regulating aggregate-based responses in yeast. Our study extends the range of responses controlled by filamentation regulatory pathways and has implications in understanding aspects of fungal biology that may be relevant to fungal pathogenesis.IMPORTANCE Filamentous growth is a fungal morphogenetic response that is critical for virulence in some fungal species. Many aspects of filamentous growth remain poorly understood. We have identified an aspect of filamentous growth in the budding yeast Saccharomyces cerevisiae and the human pathogen Candida albicans where cells behave collectively to invade surfaces in aggregates. These responses may reflect an extension of normal filamentous growth, as they share the same signaling pathways and effector processes. Aggregate responses may involve cooperation among individual cells, because aggregation was stimulated by cell adhesion molecules, secreted enzymes, and diffusible molecules that promote quorum sensing. Our study may provide insights into the genetic basis of collective cellular responses in fungi. The study may have ramifications in fungal pathogenesis, in situations where collective responses occur to promote virulence.

Dataset Information

Is Aggregate-Dependent Yeast Aging Fortuitous? A Model of Damage Segregation and Aggregate Dynamics.

Publications

Is Aggregate-Dependent Yeast Aging Fortuitous? A Model of Damage Segregation and Aggregate Dynamics.

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