Involvement of transporter recruitment as well as gene expression in the substrate-induced adaptive regulation of amino acid transport system A

Ruan Ling, Christy C. Bridges, Mitsuru Sugawara, Takuya Fujita, Frederick H. Leibach, Puttur D. Prasad, Vadivel Ganapathy

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

We investigated the molecular mechanism involved in the adaptive regulation of the amino acid transport system A, a process in which amino acid starvation induces the transport activity. These studies were done with rat C6 glioma cells. System A activity in these cells is mediated exclusively by the system A subtype, amino acid transporter A2 (ATA2). The other two known system A subtypes, ATA1 and ATA3, are not expressed in these cells. Exposure of these cells to an amino acid-free medium induces system A activity. This process consists of an acute phase and a chronic phase. Laser-scanning confocal microscopic immunolocalization of ATA2 reveals that the acute phase is associated with recruitment of preformed ATA2 from an intracellular pool to the plasma membrane. In contrast, the chronic phase is associated with an induction of ata2 gene expression as evidenced from the increase in the steady-state levels of ATA2 mRNA, restoration of the intracellular pool of ATA2 protein, and blockade of the induction by cycloheximide and actinomycin D. The increase in system A activity induced by amino acid starvation is blocked specifically by system A substrates, including the non-metabolizable α-(methylamino)isobutyric acid.

Original languageEnglish (US)
Pages (from-to)15-21
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1512
Issue number1
DOIs
StatePublished - May 2 2001

Keywords

  • Adaptive regulation
  • Amino acid starvation
  • Gene expression
  • Glioma cell
  • System A
  • Transporter recruitment

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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