YEAST SENSING

Nutrient sensing and signaling by the yeast Gap1 amino acid transceptor

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 Obiettivo del progetto (Objective)

'The proposal aims the reintegration of a senior post-doctoral researcher of Spanish nationality, Dr. Marta Rubio-Texeira, now working at the Whitehead Institute (MIT, Cambridge, MA, USA), into the European research area at VIB/KULeuven in Belgium. Dr. Rubio-Texeira has advanced knowledge and extensive technical know-how on molecular mechanisms involved in plasma membrane protein trafficking and internalization in yeast, in the use of yeast as a tool to study proteins involved in neurodegenerative diseases and in the biotechnology of lactose fermentation. She will be integrated into the VIB department of Molecular Microbiology, located at the KULeuven, as a senior post-doctoral researcher, with committed support of the FWO Flanders for her initial appointment. With her experience she will strenghten the world leading research at this department into the molecular genetics and biochemistry of nutrient sensing and signaling in yeast. She will concentrate her work on the functioning of Gap1, an amino acid transporter that also functions as an amino acid sensor for activation of the protein kinase A (PKA) pathway in yeast. Gap1 is the best established example in eukaryotic cell biology of an actively transporting nutrient carrier that also functions as a receptor protein (‘transceptor’). She will investigate the relationship between Gap1 mediated amino acid activation of the PKA pathway and the rapid amino acid induced downregulation of Gap1 by dephosphorylation, ubiquitination, internalization and degradation. The latter is reminiscent of ligand-induced downregulation that occurs in many classical receptor proteins. In the second part of her work she will focus on elucidation of the components in the signaling pathway between Gap1 and PKA. The research on yeast nutrient sensing and signaling is a long-term goal in the VIB department of Molecular Microbiology and thus offers the possibility of permanent integration into the European Research Area.'

Introduzione (Teaser)

Misregulation of the PKA pathway and of plasma membrane receptors is known to be related to a variety of disorders. These include cancer and cardiac diseases.

Descrizione progetto (Article)

Research into yeast nutrient sensing and signalling is a long-term goal at KULeuven in Belgium as it is important from both industrial and biomedical points of view.

The Yeast sensing project has so far concentrated on studying general amino acid permease (Gap1) functioning from Saccharomyces cerevisiae (budding yeast). This protein is called a transceptor as it has both transporter and receptor functions. Gap1 is also an amino acid transporter that functions as an amino acid sensor, too, for activation of the protein kinase A (PKA) pathway in yeast.

Researchers are investigating the relationship between Gap1-mediated amino acid activation of the PKA pathway, and focusing on highlighting the components in the signalling pathway between Gap1 and PKA. Analysing these mechanisms will offer new insights into how the nutrient signal is transmitted from nutrient transceptor to the central growth regulator pathway controlled by PKA.

The main achievements to date include increasing trehalase activity from about one hour to a window of three hours. In addition, this is the first time yeast has been used where conditions are shown to enable a transceptor to continue signalling after being endocytosed. One unexpected result reveals the ability of the Gap1 transceptor to take up amino acids as well as specific types of dipeptides.

Yeast sensing will continue experiments at the molecular level to gain a better understanding of how intracellular signalling actually takes place, and also how it is stopped under normal circumstances. Additional research is also being conducted to discover whether Npr1 is a substrate for PKA. This is important since Npr1 kinase activity is needed to stabilise Gap1 and other nutrient transporters at the plasma membrane.