Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling

Harinder S. Hundal, Peter M. Taylor

    Research output: Contribution to journalReview article

    190 Citations (Scopus)

    Abstract

    Hundal HS, Taylor PM. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296: E603-E613, 2009. First published January 21, 2009; doi:10.1152/ajpendo.91002.2008.-Amino acid transporters at the surface of cells are in an ideal location to relay nutritional information, as well as nutrients themselves, to the cell interior. These transporters are able to modulate signaling downstream of intracellular amino acid receptors by regulating intracellular amino acid concentrations through processes of coupled transport. The concept of dual-function amino acid transporter/receptor (or "transceptor") proteins is well established in primitive eukaryotes such as yeast, where detection of extracellular amino acid deficiency leads to upregulation of proteins involved in biosynthesis and transport of the deficient amino acid(s). The evolution of the "extracellular milieu" and nutrient-regulated endocrine controls in higher eukaryotes, alongside their frequent inability to synthesize all proteinaceous amino acids (and, hence, the requirement for indispensable amino acids in their diet), appears to have lessened the priority of extracellular amino acid sensing as a stimulus for metabolic signals. Nevertheless, recent studies of amino acid transporters in flies and mammalian cell lines have revealed perhaps unanticipated "echoes" of these transceptor functions, which are revealed by cellular stresses (notably starvation) or gene modification/silencing. APC-transporter superfamily members, including slimfast, path, and SNAT2 all appear capable of sensing and signaling amino acid availability to the target of rapamycin (TOR) pathway, possibly through PI 3-kinase-dependent mechanisms. We hypothesize (by extrapolation from knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the transceptor discriminates between extracellular and intracellular amino acid stimuli when evoking a signal.

    Original languageEnglish
    Pages (from-to)E603-E613
    Number of pages11
    JournalAmerican Journal of Physiology, Endocrinology and Metabolism
    Volume296
    Issue number4
    DOIs
    Publication statusPublished - Apr 2009

    Keywords

    • SNAT2
    • mammalian target of rapamycin
    • GCN2
    • transporters
    • receptors
    • CELL-SURFACE EXPRESSION
    • TRANSPORT SYSTEM-A
    • ACTIVATING TRANSCRIPTION FACTOR-4
    • YEAST SACCHAROMYCES-CEREVISIAE
    • HUMAN FETAL ASTROCYTES
    • SKELETAL-MUSCLE CELLS
    • GLUTAMATE TRANSPORTER
    • ADAPTIVE REGULATION
    • PLASMA-MEMBRANE
    • PROTEIN-SYNTHESIS

    Cite this

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    abstract = "Hundal HS, Taylor PM. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296: E603-E613, 2009. First published January 21, 2009; doi:10.1152/ajpendo.91002.2008.-Amino acid transporters at the surface of cells are in an ideal location to relay nutritional information, as well as nutrients themselves, to the cell interior. These transporters are able to modulate signaling downstream of intracellular amino acid receptors by regulating intracellular amino acid concentrations through processes of coupled transport. The concept of dual-function amino acid transporter/receptor (or {"}transceptor{"}) proteins is well established in primitive eukaryotes such as yeast, where detection of extracellular amino acid deficiency leads to upregulation of proteins involved in biosynthesis and transport of the deficient amino acid(s). The evolution of the {"}extracellular milieu{"} and nutrient-regulated endocrine controls in higher eukaryotes, alongside their frequent inability to synthesize all proteinaceous amino acids (and, hence, the requirement for indispensable amino acids in their diet), appears to have lessened the priority of extracellular amino acid sensing as a stimulus for metabolic signals. Nevertheless, recent studies of amino acid transporters in flies and mammalian cell lines have revealed perhaps unanticipated {"}echoes{"} of these transceptor functions, which are revealed by cellular stresses (notably starvation) or gene modification/silencing. APC-transporter superfamily members, including slimfast, path, and SNAT2 all appear capable of sensing and signaling amino acid availability to the target of rapamycin (TOR) pathway, possibly through PI 3-kinase-dependent mechanisms. We hypothesize (by extrapolation from knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the transceptor discriminates between extracellular and intracellular amino acid stimuli when evoking a signal.",
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    Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. / Hundal, Harinder S.; Taylor, Peter M.

    In: American Journal of Physiology, Endocrinology and Metabolism, Vol. 296, No. 4, 04.2009, p. E603-E613.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling

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    AU - Taylor, Peter M.

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    N2 - Hundal HS, Taylor PM. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296: E603-E613, 2009. First published January 21, 2009; doi:10.1152/ajpendo.91002.2008.-Amino acid transporters at the surface of cells are in an ideal location to relay nutritional information, as well as nutrients themselves, to the cell interior. These transporters are able to modulate signaling downstream of intracellular amino acid receptors by regulating intracellular amino acid concentrations through processes of coupled transport. The concept of dual-function amino acid transporter/receptor (or "transceptor") proteins is well established in primitive eukaryotes such as yeast, where detection of extracellular amino acid deficiency leads to upregulation of proteins involved in biosynthesis and transport of the deficient amino acid(s). The evolution of the "extracellular milieu" and nutrient-regulated endocrine controls in higher eukaryotes, alongside their frequent inability to synthesize all proteinaceous amino acids (and, hence, the requirement for indispensable amino acids in their diet), appears to have lessened the priority of extracellular amino acid sensing as a stimulus for metabolic signals. Nevertheless, recent studies of amino acid transporters in flies and mammalian cell lines have revealed perhaps unanticipated "echoes" of these transceptor functions, which are revealed by cellular stresses (notably starvation) or gene modification/silencing. APC-transporter superfamily members, including slimfast, path, and SNAT2 all appear capable of sensing and signaling amino acid availability to the target of rapamycin (TOR) pathway, possibly through PI 3-kinase-dependent mechanisms. We hypothesize (by extrapolation from knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the transceptor discriminates between extracellular and intracellular amino acid stimuli when evoking a signal.

    AB - Hundal HS, Taylor PM. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab 296: E603-E613, 2009. First published January 21, 2009; doi:10.1152/ajpendo.91002.2008.-Amino acid transporters at the surface of cells are in an ideal location to relay nutritional information, as well as nutrients themselves, to the cell interior. These transporters are able to modulate signaling downstream of intracellular amino acid receptors by regulating intracellular amino acid concentrations through processes of coupled transport. The concept of dual-function amino acid transporter/receptor (or "transceptor") proteins is well established in primitive eukaryotes such as yeast, where detection of extracellular amino acid deficiency leads to upregulation of proteins involved in biosynthesis and transport of the deficient amino acid(s). The evolution of the "extracellular milieu" and nutrient-regulated endocrine controls in higher eukaryotes, alongside their frequent inability to synthesize all proteinaceous amino acids (and, hence, the requirement for indispensable amino acids in their diet), appears to have lessened the priority of extracellular amino acid sensing as a stimulus for metabolic signals. Nevertheless, recent studies of amino acid transporters in flies and mammalian cell lines have revealed perhaps unanticipated "echoes" of these transceptor functions, which are revealed by cellular stresses (notably starvation) or gene modification/silencing. APC-transporter superfamily members, including slimfast, path, and SNAT2 all appear capable of sensing and signaling amino acid availability to the target of rapamycin (TOR) pathway, possibly through PI 3-kinase-dependent mechanisms. We hypothesize (by extrapolation from knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the transceptor discriminates between extracellular and intracellular amino acid stimuli when evoking a signal.

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    KW - GCN2

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    KW - CELL-SURFACE EXPRESSION

    KW - TRANSPORT SYSTEM-A

    KW - ACTIVATING TRANSCRIPTION FACTOR-4

    KW - YEAST SACCHAROMYCES-CEREVISIAE

    KW - HUMAN FETAL ASTROCYTES

    KW - SKELETAL-MUSCLE CELLS

    KW - GLUTAMATE TRANSPORTER

    KW - ADAPTIVE REGULATION

    KW - PLASMA-MEMBRANE

    KW - PROTEIN-SYNTHESIS

    U2 - 10.1152/ajpendo.91002.2008

    DO - 10.1152/ajpendo.91002.2008

    M3 - Review article

    C2 - 19158318

    VL - 296

    SP - E603-E613

    JO - American Journal of Physiology, Endocrinology and Metabolism

    JF - American Journal of Physiology, Endocrinology and Metabolism

    SN - 0193-1849

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    ER -