Molecular Characterization of the AKT-TOR Signaling Pathway in Rainbow Trout (Oncorhynchus mykiss): Its Potential Role in Muscle Growth and Degradation

Background: The AKT-TOR signaling pathway plays a key role in cellular metabolism and muscle growth. Endocrine, nutrition and stress factors affect the AKT-TOR pathway through regulating gene transcription and protein synthesis/degradation. In fish, little is known about the role of the AKT-TOR pathway in muscle growth and degradation.;Objectives: The objectives of this study were to: 1) identify and characterize genes in the rainbow trout AKT-TOR signaling pathway, 2) determine the in vivo expression of AKT-TOR genes associated with starvation- and vitellogenesis-induced muscle atrophy, and 3) determine the in vitro effects of insulin-like growth factor-I (IGF-I), insulin, serum starvation and dexamethasone on expression of AKT-TOR genes in primary cultures of 4-day old rainbow trout myocytes.;Results: We have identified and characterized the cDNA sequences for 7 genes in the AKT-TOR signaling pathway of rainbow trout including MAPK3, REDD1, AKT2, MO25, GβL, Rheb and eIF4B. Gene expression of the AKT-TOR signaling pathway was down-regulated in starvation- and vitellogenesis-induced muscle atrophy. Whereas, the AKT-TOR pathway was elevated in fish selected for fast growth compared to fish with slow growth rate. Western blot analysis showed down-regulation and dephosphorylation of the AKT and S6 protein in vitellogenesis-induced muscle atrophy. Dexamethasone induced a dramatic up-regulation of REDD1 gene in rainbow trout primary myocytes.;Conclusion: Gene expression data confirm the role of the AKT-TOR pathway as an important regulator of muscle growth and atrophy in rainbow trout. This study provides new information to our understanding of how the AKT-TOR pathway is regulated during muscle growth and degradation in non-mammalian species.