Cell death is a natural part of the development of multicellular organisms and is central to their physiological and pathological states. However, the existence of regulated cell death in unicellular microorganisms, including eukaryotic and prokaryotic microbes, has been a topic of debate. One reason for the continued debate is the lack of obvious benefit from cell death in the context of a single cell. However, unicellularity is relative, as most of these microbes dwell in communities of varying complexities, often with complicated spatial organization. In these spatially organized microbial communities, such as yeast and bacterial colonies and biofilms growing on solid surfaces, cells differentiate into specialized types, and the whole community often behaves like a simple multicellular organism. As these communities develop and age, cell death appears to offer benefits to the community as a whole. This review explores the potential roles of cell death in spatially organized communities of yeasts and draws analogies to similar communities of bacteria. The natural dying processes in microbial cell communities are only partially understood and may result from suicidal death genes, (self-)sabotage (without death effectors), or from non-autonomous mechanisms driven by interactions with other differentiated cells. We focus on processes occurring during the stratification of yeast colonies, the formation of the extracellular matrix in biofilms, and discuss potential roles of cell death in shaping the organization, differentiation, and overall physiology of these microbial structures.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Gcn4p belongs to conserved AP-1 transcription factors involved in many cellular processes, including cell proliferation, stress response, and nutrient availability in yeast and mammals. AP-1 activities are regulated at different levels, such as translational activation or protein degradation, which increases the variability of regulation under different conditions. Gcn4p activity in unstructured yeast liquid cultures increases upon amino acid deficiency and is rapidly eliminated upon amino acid excess. Gcn2p kinase is the major described regulator of Gcn4p that enables GCN4 mRNA translation via the uORFs mechanism. Here, we show that Gcn4p is specifically active in U cells in the upper regions and inactive in L cells in the lower regions of differentiated colonies. Using in situ microscopy in combination with analysis of mutants and strains with GFP at different positions in the translational regulatory region of Gcn4p, we show that cell-specific Gcn4p activity is independent of Gcn2p or other translational or transcriptional regulation. Genetically, biochemically, and microscopically, we identified cell-specific proteasomal degradation as a key mechanism that diversifies Gcn4p function between U and L cells. The identified regulation leading to active Gcn4p in U cells with amino acids and efficient degradation in starved L cells differs from known regulations of Gcn4p in yeast but shows similarities to the activity of AP-1 ATF4 in mammals during insulin signaling. These findings may open new avenues for understanding the parallel activities of Gcn4p/ATF4 and reveal a novel biological role for cell type-specific regulation of proteasome-dependent degradation.IMPORTANCEIn nature, microbes usually live in spatially structured communities and differentiate into precisely localized, functionally specialized cells. The coordinated interplay of cells and their response to environmental changes, such as starvation, followed by metabolic adaptation, is critical for the survival of the entire community. Transcription factor Gcn4p is responsible for yeast adaptation under amino acid starvation in liquid cultures, and its activity is regulated mainly at the level of translation involving Gcn2p kinase. Whether Gcn4p functions in structured communities was unknown. We show that translational regulation of Gcn4p plays no role in the development of colony subpopulations; the main regulation occurs at the level of stabilization of the Gcn4p molecule in the cells of one subpopulation and its proteasomal degradation in the other. This regulation ensures specific spatiotemporal activity of Gcn4p in the colony. Our work highlights differences in regulatory networks in unorganized populations and organized structures of yeast, which in many respects resemble multicellular organisms.

• Klíčová slova
• Saccharomyces cerevisiae, cell-specific regulation, differentiated colonies, proteasomal degradation, spatially structured populations, transcription factor, yeast,
• MeSH
• protein-serin-threoninkinasy metabolismus   genetika   MeSH
• proteolýza MeSH
• proteosyntéza MeSH
• regulace genové exprese u hub * MeSH
• Saccharomyces cerevisiae - proteiny * genetika   metabolismus   MeSH
• Saccharomyces cerevisiae * genetika   metabolismus   MeSH
• stabilita proteinů MeSH
• transkripční faktory bZIP * metabolismus   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• GCN2 protein, S cerevisiae MeSH Prohlížeč
• GCN4 protein, S cerevisiae MeSH Prohlížeč
• protein-serin-threoninkinasy MeSH
• Saccharomyces cerevisiae - proteiny * MeSH
• transkripční faktory bZIP * MeSH