Isp7 is a novel regulator of amino acid uptake in the TOR signaling pathway

Dana Laor1, Adiel Cohen, Metsada Pasmanik-Chor

  • 1Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel.

Insights

The study reveals that Isp7 protein regulates cellular growth and survival by influencing both TORC1 and TORC2 pathways. Overexpressing Isp7 impacts rapamycin sensitivity and amino acid homeostasis in yeast.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Target of Rapamycin (TOR) signaling pathway, comprising TOR complex 1 (TORC1) and TOR complex 2 (TORC2), is crucial for regulating cell growth, proliferation, and survival.
  • Rapamycin, an immunosuppressive and anticancer drug, targets TOR signaling.
  • Disruption of the TSC complex in Schizosaccharomyces pombe leads to rapamycin sensitivity under nutrient-poor conditions.

Purpose of the Study:

  • To investigate the role of isp7(+) in mediating rapamycin sensitivity in S. pombe.
  • To elucidate the regulatory relationship between Isp7, TORC1, and TORC2.
  • To understand Isp7's function in amino acid homeostasis and its impact on cellular processes.

Main Methods:

  • Genetic manipulation of S. pombe strains, including disruption of the TSC complex and overexpression of isp7(+).
  • Transcriptome analysis to compare gene expression profiles.
  • Assays for rapamycin sensitivity and phosphorylation of key proteins (Rps6, Gad8).

Main Results:

  • Rapamycin sensitivity in S. pombe is linked to TORC1 inhibition and can be suppressed by isp7(+) overexpression.
  • Isp7 transcript levels are differentially regulated by TORC1 (negative) and TORC2 (positive).
  • Isp7 influences amino acid permease expression similarly to TORC1 and oppositely to TORC2, affecting Rps6 and Gad8 phosphorylation.

Conclusions:

  • Isp7 plays a significant role in maintaining amino acid homeostasis.
  • Regulatory feedback loops involving isp7(+) modulate the activity of both TORC1 and TORC2.
  • Findings suggest a conserved mechanism linking TOR signaling, amino acid metabolism, and cellular growth.

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