Cell differentiation in response to nutrient availability : the repressor of meiosis, RME1, positively regulates invasive growth in Saccharomyces cerevisiae

[摘要] ENGLISH ABSTRACT:Yeasts, like most organisms, have to survive in highly variable and hostileenvironments. Survival therefore requires adaptation to the changing externalconditions. On the molecular level, specific adaptation to specific environmentalconditions requires the yeast to be able: (i) to sense all relevant environmentalparameters; (ii) to relay the perceived signals to the interior of the cell via signaltransduction networks; and (iii) to implement a specific molecular response bymodifying enzyme activities and by regulating transcription of the appropriate genes.The availability of nutrients is one of the major trophic factors for all unicellularorganisms, including yeast. Saccharomyces cerevisiae senses the nutritionalcomposition of the media and implements a specific developmental choice in responseto the level of essential nutrients. In conditions in which ample nutrients are available,S. cerevisiae will divide mitotically and populate the growth environment. If thenutrients are exhausted, diploid S. cerevisiae cells can undergo meiosis, whichproduces four ascospores encased in an ascus. These ascospores are robust andprovide the yeast with a means to survive adverse environmental conditions. Theascospores can lie dormant for extended periods of time until the onset of favourablegrowth conditions, upon which the spores will germinate, mate and give rise to a newyeast population. However, S. cerevisiae has a third developmental option, referred toas pseudohyphal and invasive growth. In growth conditions in which nutrients arelimited, but not exhausted, the yeast can undergo a morphological switch, altering itsbudding pattern and forming chains of elongated cells that can penetrate the growthsubstrate to forage for nutrients.The focus of this study was on elements of the signal transduction networksregulating invasive growth in S. cerevisiae. Some components of the signaltransduction pathways are well characterised, while several transcription factors thatare regulated via these pathways remain poorly studied. In this study, the RMEt genewas identified for its ability to enhance starch degradation and invasive growth whenpresent on a multiple copy plasmid. Rme1 p had previously been identified as arepressor of meiosis and, for this reason, the literature review focuses on theregulation of the meiotic process. In particular, the review focuses on the factorsgoverning entry into meiosis in response to nutrient starvation and ploidy. Also, thetranscriptional regulation of the master initiator of meiosis, IMEt, and the action ofIme1 p are included in the review.The experimental part of the study entailed a genetic analysis of the role of Rme1 pin invasive growth and starch metabolism. Epistasis analysis was conducted ofRme1 p and elements of the MAP Kinase module, as well as of the transcriptionfactors, Mss11p, Msn1p/Mss10p, Tec1p, Phd1p and F108p. Rme1p is known to bindto the promoter of CLN2, a G1-cyclin, and enhances its expression. Therefore, the cell cyclins CLN1 and CLN2 were included in the study. The study revealed that Rme1 pfunctions independently or downstream of the MAP Kinase cascade and does notrequire Cln1 p or Cln2p to induce invasive growth. FL011/MUC1 encodes a cell wallprotein that is required for invasive growth. Like the above-mentioned factors, Rme1 prequires FL011 to induce invasive growth. We identified an Rme1 p binding site in thepromoter of FL011. Overexpression of Rme1p was able to induce FL01t expression,despite deletions of mss11, msn1, ttos, tee1 and phd1. In the inverse experiment,these factors were able to induce FL011 expression in an rme1 deleted strain. Thiswould indicate that Rme1 p does not function in a hierarchical signalling system withthese factors, but could function in a more general role to modify transcription.

[发布机构] Stellenbosch University