Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway.

Purine nucleotides are necessary for various biological processes related to cell proliferation. Despite their importance in DNA and RNA synthesis, cellular signaling, and energy-dependent reactions, the impact of changes in cellular purine levels on cell physiology remains poorly understood. Here, we find that purine depletion stimulates cell migration, despite effective reduction in cell proliferation.

Hepatic mTORC1 signaling activates ATF4 as part of its metabolic response to feeding and insulin.

Objective: The mechanistic target of rapamycin complex 1 (mTORC1) is dynamically regulated by fasting and feeding cycles in the liver to promote protein and lipid synthesis while suppressing autophagy. However, beyond these functions, the metabolic response of the liver to feeding and insulin signaling orchestrated by mTORC1 remains poorly defined. Here, we determine whether ATF4, a stress responsive transcription factor recently found to be independently regulated by mTORC1 signaling in proliferating cells, is responsive to hepatic mTORC1 signaling to alter hepatocyte metabolism.

The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels.

Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. We find that the mTORC1 pathway is responsive to changes in purine nucleotides in a manner analogous to its sensing of amino acids. Depletion of cellular purines, but not pyrimidines, inhibits mTORC1, and restoration of intracellular adenine nucleotides via addition of exogenous purine nucleobases or nucleosides acutely reactivates mTORC1.

OPHIDIOMYCES OPHIODIICOLA ON A CAPTIVE BLACK RACER (COLUBER CONSTRICTOR) AND A GARTER SNAKE (THAMNOPHIS SIRTALIS) IN PENNSYLVANIA.

Two snakes were presented to the Pennsylvania State University Animal Diagnostic Laboratory with one suffering from external lesions where the scales were raised and discolored, and the other with oral lesions and swelling extending to the left eye, which was opaque. Histopathological analysis revealed multifocal granulomas containing fungal hyphae. Morphological and DNA sequence analyses revealed both suffered from infection by Ophidiomyces ophiodiicola, an emerging pathogen of snakes.

Snf1/AMPK promotes the formation of Kog1/Raptor-bodies to increase the activation threshold of TORC1 in budding yeast.

The target of rapamycin complex I (TORC1) regulates cell growth and metabolism in eukaryotes. Previous studies have shown that nitrogen and amino acid signals activate TORC1 via the small GTPases, Gtr1/2. However, little is known about the way that other nutrient signals are transmitted to TORC1.

State transitions in the TORC1 signaling pathway and information processing in Saccharomyces cerevisiae.

TOR kinase complex I (TORC1) is a key regulator of cell growth and metabolism in all eukaryotes. Previous studies in yeast have shown that three GTPases-Gtr1, Gtr2, and Rho1-bind to TORC1 in nitrogen and amino acid starvation conditions to block phosphorylation of the S6 kinase Sch9 and activate protein phosphatase 2A (PP2A). This leads to downregulation of 450 Sch9-dependent protein and ribosome synthesis genes and upregulation of 100 PP2A-dependent nitrogen assimilation and amino acid synthesis genes.