Transmembrane signalling in Saccharomyces cerevisiae

Abstract

Baker's yeast, a unicellular eukaryote, has been a model organism for biochemists, geneticists and most recently for molecular biologists. Pioneering biochemical studies were conducted on yeast, such as the study of glucose fermentation and amino acid metabolism. The powerful tools of yeast genetics have allowed a comprehensive study of important issues such as the cell cycle and meiosis. In recent years, it has been established that Saccharomyces cerevisiae, the most extensively characterized of the yeasts, shares key molecules and biochemical pathways with higher eukaryotes. For example, actin, tubulin, ubiquitin, calmodulin, GTP regulatory proteins, different protein kinases including protein tyrosine kinases, were all found to play central roles in yeast [1,2]. Furthermore, structurally homologous proteins [3,4,5], as well as transcription regulating elements [6,7], of yeast and higher eukaryotes, including mammals, were shown to be structurally and functionally interchangeable. It has also been found that yeast can express human genes [8]. Technically, yeasts are simple to handle, inexpensive to grow, complete a cell cycle within 90 min, and therefore can yield relatively quick results. These qualities are useful in biotechnological applications. Saccharomyces cerevisiae, can be genetically manipulated fairly easily, and has been tinkered with more than any other system. A cloned, in vitro mutated gene, can be transformed into wild type yeast and by homologous recombination, can replace the native gene and generate the desired mutant [9]. Such manipulations, not possible yet in other eukaryotic cells, allow the precise definition of the role played by different genes and their domains. These unique features of Saccharomyces cerevisiae, together with rapidly evolving techniques of molecular biology, have made it a successful model organism for the study of numerous questions. It is a key cell in the study of major issues in biology since it provides an in vivo model where specific systems can be dissected and analysed. Combining genetic manipulations, molecular biology techniques and biochemical tools, in ways as yet not possible in other eukaryotes, has allowed the more precise treatment of problems such as the cell cycle, meiosis and secretion. Like other unicellular organisms, yeast cells respond individually to the environment. Changes in temperature, pH, cell density, oxygen pressure and especially changes in the availability of nutrients, have dramatic and rapid effects on yeast metabolism and, as a result, on the yeast cell cycle. For example, replacement of glucose by ethanol as the carbon source results in enhanced gluconeogenesis and suppression of glycolysis within seconds [10]. Depletion of glucose from the yeast culture blocks all biochemical pathways involved in the ‘start’ of cell cycle and the cells arrest at the G1 stage within 2 h [reviewed in 11]. Diploid cells undergo meiosis in response to glucose and nitrogen starvation. The cell cycle can also be controlled by mating pheromones secreted into the medium by haploid cells. MATa and MATα cells secrete a-factor and α-factor, respectively, which bind to specific receptors on the opposite mating type cell membrane. Pheromone binding causes cell cycle arrest in G1. This device allows the two mating type cells (MATa and MATα) to synchronize, mate and exchange genetic material [12, 13]. These biochemical events, triggered in response to environment, are similar to those encountered in higher eukaryotic cells. This analogy attracted many investigators of transmembrane signalling, since in yeast, one can exploit in a more definitive fashion genetic manipulations and the tools of molecular biology to elucidate the mechanism of transmembrane signalling. It is likely that understanding the details of transmembrane signalling in yeast can advance the research tools as well as the thinking on transmembrane signalling in more complex eukaryotic cells.