Amino Acid Transporters: Roles for Nutrition and Signalling in Developing Tissues

Amino acids serve both to nourish and signal in cells and, consequently, so do their biomembrane transporters. Most amino acid transporters now appear to have been cloned, and virtually all of the cloned transporters are listed in solute carrier (SLC) tables for easy access online (http://www.bioparadigms.org/slc/menu.asp). It is more difficult to decide which transporters are expressed in a given tissue, and the tissue's transporter functions will likely continue to emerge long after all of the transporters have been identified. We illustrate these ongoing investigations of transporter identification and function for the first cell types to differentiate in the early embryo.

Keywords: amino acid transport systems; blastocyst; trophoblasts; blastocyst inner cell mass; embryonic stem cells

Figure 1. One-cell embryos that do not express the slc7a2 product (CAT2 knockout embryos) have reduced system b+1 activity relative to one-cell embryos from genetically similar control mice. CAT2 knockout mice (and embryos) do not express a functional CAT2 protein (slc7a2 product). System b+1 activity was measured as defined previously (Van Winkle, 2001). The mean (±S.E.) activities shown were each calculated from 6–13 determinations obtained in 3–6 independent experiments. The total system b+1 activity in one-cell embryos from CAT2 knockout mice was significantly lower than the activity in embryos from otherwise genetically similar control mice as determined in a group comparison t-test (p<0.01). The reduction in activity is attributed to the lack of functional CAT2 expression, whereas the activity remaining in one-cell embryos from CAT2 knockout mice is attributed to CAT1 (slc7a1 product) and, possibly, CAT3 (slc7a3 product) expression (Table 1). CAT1, CAT2 and probably CAT3 normally are expressed throughout preimplantation development. The lack of reduction in system b+1 activity in CAT2 knockout two-cell conceptuses is attributed to increased expression of CAT1 or CAT3 upon activation of the embryo genome at the late one-cell stage to compensate for the missing CAT2 activity. See text for further discussion.
Figure 2. Changes in the aspartate (Asp), glutamate (Glu) and glutamine (Gln) content of pre-implantation mouse embryos during development in vivo. Stages of development at various times after fertilization are: 35 h=2-cell, 59 h=4- to 8-cell, 83 h=earlier blastocyst and 107 h=later blastocyst. (Data from Tables 2 and 5 of Van Winkle and Dickinson, 1995).
close
 References
    Hediger MA, Romero MF, Peng J-B et al. (2004) The ABC's of solute carriers: physiological, pathophysiological and therapeutic implications of human membrane transport proteins. Pflugers Archives 447: 465–468.
    Idris Anas MA, Hammer MA, Lever M, Stanton JA and Baltz JM (2007) The organic osmolytes betaine and proline are transported by a shared system in early preimplantation mouse embryos. Journal of Cellular Physiology 210: 266–277.
    book Kilberg MS and Matthews JC (2001) "Amino acid transporters". In: Cox M (ed.) Encyclopedia of Life Sciences. www.els.net. West Sussex, UK: John Wiley & Sons Ltd.
    Martin PM, Sutherland AE and Van Winkle LJ (2003) Amino acid transport regulates blastocyst implantation. Biology of Reproduction 69: 1101–1108.
    Nakajo T, Yamatsuji T, Ban H et al. (2005) Glutamine is a key regulator for amino acid-controlled cell growth through the mTOR signaling pathway in rat intestinal epithelial cells. Biochemical and Biophysical Research Communications 326: 174–180.
    Sobczak I and Lolkema JS (2005) Structural and mechanistic diversity of secondary transporters. Current Opinion in Microbiology 8: 161–167.
    Spinsanti P, De Vita T, Di Castro S et al. (2006) Endogenously activated mGlu5 metabotropic glutamate receptors sustain the increase in c-Myc expression induced by leukaemia inhibitory factor in cultured mouse embryonic stem cells. Journal of Neurochemistry 99: 299–307.
    book Van Winkle LJ (1999) Biomembrane Transport. San Diego, CA: Academic Press.
    Van Winkle LJ (2001) Amino acid transport regulation and early embryo development. Biology of Reproduction 64: 1–12.
    Van Winkle LJ and Dickinson HR (1995) Differences in amino acid content of preimplantation mouse embryos that develop in vitro versus in vivo: in vitro effects or five amino acids that are abundant in oviductal secretions. Biology of Reproduction 52: 96–104.
    Van Winkle LJ, Tesch JK, Shah A and Campione AL (2006) System Bo,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term development consequences through adulthood. Human Reproduction Update 12: 145–157.
 Further Reading
    Baumann CG, Morris DG, Sreenan JM and Leese HJ (2007) The quiet embryo hypothesis: molecular characteristics favoring viability. Molecular Reproduction and Development 19 [Epub ahead of print Mar 6, 2007].
    other Broer S (2007) Amino acid transport across mammalian intestinal and renal epithelia. Physiological Reviews (in press).
    Deves R and Boyd CA (2000) Surface antigen CD98 (4F2): not a single membrane protein, but a family of proteins with multiple functions. Journal of Membrane Biology 173: 165–177.
    Ganapathy ME and Ganapathy V (2005) Amino acid transporter ATBo,+ as a delivery system for drugs and prodrugs. Current Drug Targets-Immune, Endocrine & Metabolic Disorders 5: 357–364.
    Palacin M, Nunes V, Font-Llitjos M et al. (2005) The genetics of heteromeric amino acid transporters. Physiology 20: 112–124.
    Rothenberg ME, Doepker MP, Lewkowich IP et al. (2006) Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung. Proceedings of the National Academy of Sciences of the USA 103: 14895–14900.
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Van Winkle, Lon J(Dec 2007) Amino Acid Transporters: Roles for Nutrition and Signalling in Developing Tissues. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000011.pub2]