Regulation of Amino Acid Transport in Saccharomyces cerevisiae

Abstract

SUMMARY We review the mechanisms responsible for amino acid homeostasis in Saccharomyces cerevisiae and other fungi. Amino acid homeostasis is essential for cell growth and survival. Hence, the de novo synthesis reactions, metabolic conversions, and transport of amino acids are tightly regulated. Regulation varies from nitrogen pool sensing to control by individual amino acids and takes place at the gene (transcription), protein (posttranslational modification and allostery), and vesicle (trafficking and endocytosis) levels. The pools of amino acids are controlled via import, export, and compartmentalization. In yeast, the majority of the amino acid transporters belong to the APC (amino acid-polyamine-organocation) superfamily, and the proteins couple the uphill transport of amino acids to the electrochemical proton gradient. Although high-resolution structures of yeast amino acid transporters are not available, homology models have been successfully exploited to determine and engineer the catalytic and regulatory functions of the proteins. This has led to a further understanding of the underlying mechanisms of amino acid sensing and subsequent downregulation of transport. Advances in optical microscopy have revealed a new level of regulation of yeast amino acid transporters, which involves membrane domain partitioning. The significance and the interrelationships of the latest discoveries on amino acid homeostasis are put in context.

Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids

“…First, we used live cell fluorescence microscopy to analyze in yeast cells the localization of 149 putative PM proteins that were C-terminally GFP-tagged at their native chromosomal locus ( Saier et al, 2016 ; Babu et al, 2012 ; Breker et al, 2014 ; Huh et al, 2003 ). This collection included 16 different amino acid transporters (AATs) out of the 21 AATs that localize to the PM ( Bianchi et al, 2019 ). In cells growing exponentially under defined (rich) conditions, we detected 50 GFP-tagged proteins at the PM, including eight different AATs and six different carbohydrate transporters ( Figure 1A , Figure 1—figure supplement 1A , Supplementary file 1 ).…”

“…The mechanisms for the endocytic down-regulation of AATs are beginning to emerge in the budding yeast, S. cerevisiae . Yeast cells frequently experience acute fluctuations in amino acid availability ( Broach, 2012 ) and can rapidly remodel their 21 PM-localized AATs to optimize the import of amino acids with regard to the quantity and quality of the nitrogen source available ( Grenson et al, 1966 ; Grenson, 1966 ; André, 2018 ; Van Belle and André, 2001 ; Bianchi et al, 2019 ). The selective, ubiquitin-dependent endocytosis of AATs and other integral PM proteins frequently requires the HECT-type ubiquitin ligase Rsp5, the orthologue of human Nedd4 ( Hein et al, 1995 ; Dupré et al, 2004 ; Belgareh-Touzé et al, 2008 ).…”

Proteome reallocation from amino acid biosynthesis to ribosomes enables yeast to grow faster in rich media

“…S12 A ), but low uptake when it was supplemented. Uptake of glycine could possibly be achieved through the Dip5p transporter ( 38 ), which was significantly up-regulated upon supplementation in aerobic cultures ( SI Appendix , Fig. S4 C ).…”

Extracellular loops matter – subcellular location and function of the lysine transporter Lyp1 from Saccharomyces cerevisiae

“…The transport of amino acids in Saccharomyces cerevisiae is facilitated by yeast amino acid transporters (YATs) [1], which are members of the APC superfamily. The transport of amino acids is part of the cell's nitrogen regulation and biosynthesis pathways [2].…”