[Frontiers in Bioscience 16, 1445-1460, January 1, 2011]

Regulation of protein synthesis by amino acids in muscle of neonates

Agus Suryawan, Teresa A. Davis

United States Department Of Agriculture/Agriculture Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Regulation of protein synthesis in skeletal muscle of neonates
3.1. Effect of amino acids on protein synthesis in skeletal muscle of neonates
3.2. Amino acid-induced activation of signaling components leading to mRNA translation in skeletal muscle of neonates
4. Amino acid sensing mechanisms that regulate mTORC1
4.1. Role of amino acid transporters in the modulation of mTORC1 activation
4.1.1. SNAT2
4.1.2. LAT1
4.1.3. PAT
4.2. Role of amino acids in the activation of putative intracellular regulators of mTORC1
4.2.1. Raptor
4.2.2. Rheb
4.2.3. MAP4K3
4.2.4. Vps34
4.2.5. Rag GTPases
5. Amino acid sensing mechanisms that regulate translation initiation and elongation
6. Summary and perspectives
7. Acknowledgements
8. References

1. ABSTRACT

The marked increase in skeletal muscle mass during the neonatal period is largely due to a high rate of postprandial protein synthesis that is modulated by an enhanced sensitivity to insulin and amino acids. The amino acid signaling pathway leading to the stimulation of protein synthesis has not been fully elucidated. Among the amino acids, leucine is considered to be a principal anabolic agent that regulates protein synthesis. mTORC1, which controls protein synthesis, has been implicated as a target for leucine. Until recently, there have been few studies exploring the role of amino acids in enhancing muscle protein synthesis in vivo. In this review, we discuss amino acid-induced protein synthesis in muscle in the neonate, focusing on current knowledge of the role of amino acids in the activation of mTORC1 leading to mRNA translation. The role of the amino acid transporters, SNAT2, LAT1, and PAT, in the modulation of mTORC1 activation and the role of amino acids in the activation of putative regulators of mTORC1, i.e., raptor, Rheb, MAP4K3, Vps34, and Rag GTPases, are discussed.