Program Income: Regulation of EAAC1 Controllers to Enable Efficient Nutrient Metabolism

Improvement of nutrient use in production species is hindered by limited mechanistic knowledge of how transport capacity is regulated. ADP-ribosylation factor-like 6 interacting protein 1 (ARL6IP1) binds and inhibits glutamate transporter-associated protein 3-18 (GTRAP3-18), which in turn binds and inhibits EAAC1 (a concentrative glutamate/aspartate transporter; system X-AG). The ARL6IP1/GTRAP3-18/EAAC1 triad is highly expressed in rodent tissues with high glutamine and glutathione synthesis. This project will determine if the pattern and functional consequence of expressed triad proteins change as compositional gains in cattle and pigs shift from predominantly lean (LEAN) to predominantly lipid (LIPID) deposition. The specific objectives are to test the hypotheses that (1) the relative contents of GTRAP3-18 and ARL6IP1 protein and mRNA in liver, skeletal muscle, and adipose tissues of growing barrows and steers are inversely related during LEAN (n = 8) and LIPID (n = 8) growth phases, (2) system X-AG uptake activity in hepatic plasma (sinusoidal) membranes, and (3) hepatic glutamine synthetase activity and glutathione content, will be inversely proportional to GTRAP3-18 content, and greater in LIPID versus LEAN barrows and steers. This cellular- and molecular-based project will extend and elaborate rodent-based knowledge to two economically-important production species by yielding novel mechanistic knowledge to increase the efficiency of nutrient uptake and metabolism, resulting in improved performance (a biological and economic benefit) and diminished animal waste (an environmental benefit). Thus, this project immediately addresses the "nutrient utilization and efficiency" priority in the Animal, Growth, and Lactation program area of the 2013 Foundational Program.