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Role of mTOR signaling in intestinal cell migration

J Marc Rhoads1, Xiaomei Niu, Jack Odle

  • 1Div. of Gastroenterology, Dept. of Pediatrics, Univ. of Texas Medical School at Houston, 6431 Fannin St., MSB 7.137, Houston, TX 77030, USA. J.Marc.Rhoads@uth.tmc.edu

American Journal of Physiology. Gastrointestinal and Liver Physiology
|May 20, 2006
PubMed

Insights

Amino acids like L-arginine activate the mTOR/p70s6k pathway, which is crucial for protein synthesis and intestinal cell migration, potentially aiding in gut repair.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Gastroenterology

Background:

  • The mammalian target of rapamycin (mTOR) pathway regulates protein synthesis and cell growth.
  • Intestinal cell migration is vital for epithelial restitution and gut repair.
  • L-arginine (ARG) has been previously shown to enhance intestinal cell migration.

Purpose of the Study:

  • To investigate the role of the mTOR/p70s6k pathway in intestinal cell migration.
  • To determine if L-arginine activates mTOR/p70s6k signaling in migrating enterocytes.
  • To elucidate the involvement of protein synthesis and intracellular calcium in ARG-stimulated migration.

Main Methods:

  • Utilized amino acids, ARG, IGF-1, and serum to stimulate intestinal cell migration.
  • Employed mTOR/p70s6k pathway inhibitors (rapamycin, wortmannin) and calcium chelation.
  • Assessed protein synthesis requirements for cell migration.
  • Performed immunocytochemistry to localize p70s6k and phospho-p70s6k in enterocytes.

Main Results:

  • Protein synthesis is a prerequisite for intestinal cell migration.
  • Inhibition of the mTOR/p70s6k pathway significantly reduced cell migration.
  • ARG activated both cell migration and the mTOR/p70s6k pathway in enterocytes.
  • Phospho-p70s6k localization shifted from the nucleus to the cell periphery upon ARG activation.

Conclusions:

  • The mTOR/p70s6k signaling pathway is essential for intestinal cell migration.
  • L-arginine activates this pathway, influencing both nuclear and cytoplasmic events.
  • This pathway may represent a therapeutic target for promoting intestinal repair.

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