Journal of Molecular Neuroscience

, Volume 16, Issue 2–3, pp 133–142 | Cite as

Fatty acid-binding proteins of nervous tissue

Article

Abstract

Fatty acid-binding proteins (FABPs) are cytosolic 14–15 kDa proteins, which are supposed to be involved in fatty acid (FA) uptake, transport, and targeting. They may modulate FA concentration and in this way influence function of enzymes, membranes, ion channels and receptors, and gene expression and cellular growth and differentiation. Nine FABP types can be discerned with a specific tissue distribution. In spite of 30–70% amino acid sequence identity, they have a similar tertiary, β-clam structure in which the FA is bound.

Nervous tissue contains four FABP types with a distinct spatio-temporal distribution. Myelin (M)-FABP is only present in the peripheral nerves, brain (B)-FABP and epidermal (E)-FABP mainly in glial cells and neurons, respectively of pre- and perinatal brain, and heart (H)-FABP in adult brain. Possible functions of FABPs in the nervous system are discussed.

Binding studies with a range of physiological FA showed no large differences between recombinant proteins of the four human FABP types in binding specificity and affinity, also not for polyunsaturated FA (PUFA). The transfer of FA from fixed liposomes to mitochondria was similarly promoted by the four types. A marked difference in conformational stability was observed with H-FABP > B-FABP > M-FABP > E-FABP. Surface epitopes of H-FABP showed reaction with anti-B-FABP antibodies, but no other cross-reactivity of FABP type and heterologous antibodies was observed. The functional significance of the distinct spatio-temporal pattern of the four FABP types remains to be elucidated.

Index Entries

Myelin FABP brain FABP protein-ligand interactions spatio-temporal distribution conformational stability cross-reactivity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abumrad N., Coburn C., and Ibrahimi A. (1999) Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm. Biochim. Biophys. Acta 1441, 4–13.PubMedGoogle Scholar
  2. Allen G. W., Liu J-W., and De León M. (2000) Depletion of a fatty acid-binding protein impaires neurite outgrowth in PC12 cells. Mol. Brain Res. 76, 315–324.PubMedCrossRefGoogle Scholar
  3. Banaszak L., Winter N., Xu Z., Bernlohr D. A., Cowan S., and Jones, T. A. (1994) Lipid-binding proteins: a family of fatty acid and retinoid transport proteins. Adv. Prot. Chem. 45, 89–151.CrossRefGoogle Scholar
  4. Bass N. M., Raghupathy E., Rhoads D. E., Manning J. A., and Ockner R. K. (1984) Partial purification of molecular weight 12000 fatty acid binding proteins from rat brain and their effect on synaptosomal Na+-dependent amino acid uptake. Biochemistry 23, 6539–6544.PubMedCrossRefGoogle Scholar
  5. Bennett E., Stenvers K. L, Lund P. K., and Popko B. (1994) Cloning and characterization of a cDNA encoding a novel fatty acid binding protein from rat brain. J. Neurochem. 63, 1616–1624.PubMedCrossRefGoogle Scholar
  6. Bernlohr D. A., Simpson M. A., Vogel Hertzel A., and Banaszak L. J. (1997) Intracellular lipid-binding proteins and their genes. Annu. Rev. Nutr. 17, 277–303.PubMedCrossRefGoogle Scholar
  7. De León M., Welcher A. A., Liu N. Y., Ruda M. A., Shooter E. M., and Molina C. A. (1996) Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury. J. Neurosci. Res. 44, 283–292.PubMedCrossRefGoogle Scholar
  8. Desvergne B., Ijpenberg A., Devchand P. R., and Wahli W. (1998) The peroxisome proliferator-activated receptors at the cross-road of diet and hormonal signalling. J. Steroid Biochem. Mol. Biol. 65, 65–74.PubMedCrossRefGoogle Scholar
  9. Eylar E. H., Szymanska I., Ishaque A., Ramwani J., and Dubiski S. (1980) Localization of the P2 protein in peripheral nerve myelin. J. Immunol. 124, 1086–1092.PubMedGoogle Scholar
  10. Faroqui J. Z., Robb E., Boyce S. T., Warde G. D., and Nordlund J. J. (1995) Isolation of a unique melanogenic inhibitor from human skin xenografts: initial in vitro and in vivo characterization. J. Invest. Dermatol. 104, 739–743.CrossRefGoogle Scholar
  11. Feng L., Hatten M. E., and Heintz N. (1994) Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS. Neuron 12, 895–908.PubMedCrossRefGoogle Scholar
  12. Feng L. and Heintz N. (1995) Differentiating neurons activate transcription of the brain lipid-binding protein gene in radial glia through a novel regulatory element. Development 121, 1719–1730.PubMedGoogle Scholar
  13. Glatz J. F. C. and van der Vusse G. J. (1996) Cellular fatty acid-binding proteins: their function and physiological significance. Prog. Lipid Res. 35, 243–282.PubMedCrossRefGoogle Scholar
  14. Godbout R., Marusyk H., Bisgrove D., Dabbagh L., and Poppema S. (1995) Localization of a fatty acid binding protein and its transcript in the developing chick retina. Exp. Eye Res. 60, 645–657.PubMedCrossRefGoogle Scholar
  15. Godbout R., Bisgrove D. A., Shkolny D., and Day R. S. (1998) Correlation of B-FABP and GFAP expression in malignant glioma. Oncogene 16, 1955–1962.PubMedCrossRefGoogle Scholar
  16. Green P., Glozman S., Kamensky B., and Yavin E. (1999) Developmental changes in rat brain membrane lipids and fatty acids: the preferential prenatal accumulation of docosaheaenoic acid. J. Lipid Res. 40, 960–966.PubMedGoogle Scholar
  17. Grimaldi P. A., Teboul L., Gaillard D., Armengod A. V., and Amri E. Z. (1999) Long chain fatty acids as modulators of gene transcription in preadipose cells. Mol. Cell. Biochem. 192, 63–68.PubMedCrossRefGoogle Scholar
  18. Hamilton J.A. and Kamp F. (1999) How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids? Diabetes 48, 2255–2269.PubMedCrossRefGoogle Scholar
  19. Heuckeroth R. O, Birkenmeier E. H., Levin M. S., and Gordon J. I. (1987) Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein. J. Biol. Chem. 262, 9709–9717.PubMedGoogle Scholar
  20. Hohoff C. and Spener F. (1998) Fatty acid binding proteins and mammary-derived growth inhibitor. Fett (Lipid) 6, 252–263.CrossRefGoogle Scholar
  21. Hohoff C., Börchers T., Rüstow B., Spener F., and van Tilbeurgh H. (1999) Expression, purification, and crystal structure determination of recombinant human epidermal-type fatty acid binding protein. Biochemistry 38, 12,229–12,239.CrossRefGoogle Scholar
  22. Huynh H. T., Larsson C., Narod S., and Pollak M. (1995) Tumor suppressor activity of the gene encoding mammary-derived growth inhibitor. Cancer Res. 55, 2225–2231.PubMedGoogle Scholar
  23. Jump D. B. and Clarke S. D. (1999) Regulation of gene expression by dietary fat. Annu. Rev. Nutr. 19, 63–90.PubMedCrossRefGoogle Scholar
  24. Kane C. D., Ribarik Coe N., Vanlandingham B., Krieg P., and Bernlohr D. A. (1996) Expression, purification, and ligand-binding analysis of recombinant keratinocyte lipid-binding protein (MAL-1), an intracellular lipid-binding protein found overexpressed in neoplastic skin cells. Biochemistry 35, 2895–2900.Google Scholar
  25. Keler T. and Sorof S. (1993) Growth promotion of transfected hepatoma cells by liver fatty acid binding protein. J. Cell. Physiol. 157, 33–40.PubMedCrossRefGoogle Scholar
  26. Kingma P., Bok D., and Ong D. E. (1998) Bovine epidermal fatty acid-binding protein: determination of ligand specificity and cellular localization in retina and testis. Biochemistry 37, 3250–3257.PubMedCrossRefGoogle Scholar
  27. Kurtz A., Zimmer A., Schnütgen F., Brüning G., Spener F., and Müller T. (1994) The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development. Development 120, 2637–2649.PubMedGoogle Scholar
  28. Liu Y., Molina C. A., Welcher A. A., Longo L. D., and De León M. (1997) Expression of DA11, a neuronal-injury-induced fatty acid binding protein, coincides with axon growth and neuronal differentiation during central nervous system development. J. Neurosci. Res. 48, 551–562.PubMedCrossRefGoogle Scholar
  29. Liu Y., Longo L. D., and De León M. (2000) In situ and immunocytochemical localization of E-FABP mRNA and protein during neuronal migration and differentiation in the rat brain. Brain Res. 852, 16–27.PubMedCrossRefGoogle Scholar
  30. Maatman R. G. H. J., van Moerkerk H. T. B., Nooren I. M. A., van Zoelen E. J. J., and Veerkamp J. H. (1994) Expression of human liver fatty acid-binding protein in Escherichia coli and comparative analysis of its binding characteristics with muscle fatty acid-binding protein. Biochim. Biophys. Acta 1214, 1–10.PubMedGoogle Scholar
  31. Martin G., Schoonjans K., Lefebvre A., Staels B., and Auwerx J. (1997) Coordinate regulation of the expression of the fatty aid transport protein and acyl-CoA synthetase genes by PPARα and PPARγ activators. J. Biol. Chem. 272, 28,210–28,217.Google Scholar
  32. Masouyé I., Hagens G., van Kuppevelt T. H., Madsen P., Saurat J-H., Veerkamp J. H., et al. (1997) Endothelial cells of the human microvasculature express epidermal fatty acid-binding protein. Circ. Res. 81, 297–303.PubMedGoogle Scholar
  33. Narayanan V., Barbosa E., Reed R., and Tennekoon G. (1988) Characterization of a cloned cDNA encoding rabbit myelin P2 protein. J. Biol. Chem. 263, 8322–8337.Google Scholar
  34. Nunez E. A. (1997) Fatty acids involved in signal crosstalk between cell membrane and nucleus. Prostaglandins Leukot. Essent. Fatty Acids 57, 429–434.CrossRefGoogle Scholar
  35. Owada Y., Yoshimoto T., and Kondo H. (1996a) Spatiotemporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J. Chem. Neuroanat. 12, 113–122.PubMedCrossRefGoogle Scholar
  36. Owada Y., Yoshimoto T., and Kondo H. (1996b) Increased expression of the mRNA for brain- and skin-type but not heart-type fatty acid binding proteins following kainic acid systemic administration in the hippocampal glia of adult rats. Mol. Brain Res. 42, 156–160.PubMedCrossRefGoogle Scholar
  37. Owada Y., Utsunomiya A., Yoshimoto T., and Kondo H. (1997) Changes in gene expression for skin-type fatty acid binding protein in hypoglossal motor neurons following nerve crush. Neurosci. Letters 223, 25–28.CrossRefGoogle Scholar
  38. Paulussen R. J. A., Geelen M. J. H., Beynen A. C., and Veerkamp J. H. (1989) Immunochemical quantitation of fatty-acid-binding proteins. I. Tissue and intracellular distribution, postnatal development and influence of physiological conditions on rat heart and liver FABP. Biochim. Biophys. Acta 1001, 201–209.PubMedGoogle Scholar
  39. Prinsen C. F. M. and Veerkamp J. H. (1998) Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion. Biochem. J. 329, 265–273.PubMedGoogle Scholar
  40. Ribarik Coe N. and Bernlohr D. A. (1998) Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim. Biophys. Acta 1391, 287–306.Google Scholar
  41. Richieri G. V. and Kleinfeld A. M. (1995) Unbound free fatty acid levels in human serum. J. Lipid Res. 36, 229–240.PubMedGoogle Scholar
  42. Richieri G. V., Ogata R. T., and Kleinfeld A. M. (1994) Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB. J. Biol. Chem. 269, 23,918–23,930.Google Scholar
  43. Richieri G. V., Ogata R. T., and Kleinfeld A. M. (1999) The measurement of free fatty acid concentration with the fluorescent probe ADIFAB: a practical guide for the use of the ADIFAB probe. Mol. Cell. Biochem. 192, 87–94.PubMedCrossRefGoogle Scholar
  44. Richieri G. V., Ogata R. T., Zimmerman A. W., Veerkamp J. H., and Kleinfeld A. M. (2000) Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions. Biochemistry (in press).Google Scholar
  45. Rolf B., Oudenampsen-Krüger E., Börchers T., Færgeman N. J., Knudsen J., Lezius A., and Spener F. (1995) Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein. Biochim. Biophys. Acta 1259, 245–253.PubMedGoogle Scholar
  46. Schnütgen F., Börchers T., Müller T., and Spener F. (1996) Heterologous expression and characterization of mouse brain fatty acid binding protein. Biol. Chem. Hoppe-Seyler 377, 211–215.PubMedGoogle Scholar
  47. Schoentgen F., Pignède G., Bonanno L. M., and Jollès P. (1989) Fatty acid-binding protein from bovine brain. Amino acid sequence and some properties. Eur. J. Biochem. 185, 35–40.PubMedCrossRefGoogle Scholar
  48. Schoonjans K., Staels B., and Auwerx J. (1996) The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta 1302, 93–109.PubMedGoogle Scholar
  49. Sellner P. A., Chu W., Glatz J. F. C., and Berman N. E. J. (1995) Developmental role of fatty acid-binding proteins in mouse brain. Dev. Brain Res. 89, 33–46.CrossRefGoogle Scholar
  50. Senjo M., Ishibashi T., Imai Y., Takahashi K., and Ono T. (1985) Isolation and characterization of fatty acid-binding protein from rat brain. Arch. Biochem. Biophys. 236, 662–668.PubMedCrossRefGoogle Scholar
  51. Specht B., Bartetzko N., Hohoff C., Kuhl H., Franke R., Börchers T., and Spener F. (1996) Mammary derived growth inhibitor is not a distinct protein but a mix of heart-type and adipocyte-type fatty acid-binding protein. J. Biol. Chem. 271, 19,943–19,949.Google Scholar
  52. Thompson J., Ory J., Reese-Wagoner A., and Banaszak L. (1999) The liver fatty acid binding protein — comparison of cavity properties of intracellular lipid-binding proteins. Mol. Cell. Biochem. 192, 9–16.PubMedCrossRefGoogle Scholar
  53. Trapp B. D., Dubois-Dalcq M., and Quarles R. H. (1984) Ultrastructural localization of P2 protein in actively myelinating rat Schwann cells. J. Neurobiochem. 43, 944–948.CrossRefGoogle Scholar
  54. Utsonomiya A., Owada Y., Yoshimoto T., and Kondo H. (1997) Localization of mRNA for fatty acid transport protein in developing and mature brain of rats. Mol. Brain Res. 46, 217–222.CrossRefGoogle Scholar
  55. Veerkamp J. H. (1995) Fatty acid transport and fatty acid-binding proteins. Proc. Nutr. Soc. 54, 23–37.PubMedCrossRefGoogle Scholar
  56. Veerkamp J. H., van Moerkerk H. T. B., Glatz J. F. C., and van Hinsbergh V. W. M. (1983) Incomplete palmitate oxidation in cell-free systems of rat and human muscles. Biochim. Biophys. Acta 753, 399–410.PubMedGoogle Scholar
  57. Veerkamp J. H. and Maatman R. G. H. J. (1995) Cytoplasmic fatty acid-binding proteins: their structure and genes. Prog. Lipid Res. 34, 17–52.PubMedCrossRefGoogle Scholar
  58. Veerkamp J. H., Peeters R. A., and Maatman R. G. H. J. (1991) Structural and functional features of different types of cytoplasmic fatty acid-binding proteins. Biochim. Biophys. Acta 1081, 1–24.PubMedGoogle Scholar
  59. Veerkamp J. H., van Kuppevelt T. H. M. S. M., Maatman R. G. H. J., and Prinsen C. F. M. (1993) Structural and functional aspects of cytosolic fatty acid-binding proteins. Prostaglandins Leukot. Essent. Fatty Acids 49, 887–906.PubMedCrossRefGoogle Scholar
  60. Veerkamp J. H., van Moerkerk H. T. B., Prinsen C. F. M., and van Kuppevelt T. H. (1999) Structural and functional studies on different human FABP types. Mol. Cell. Biochem. 192, 137–142.PubMedCrossRefGoogle Scholar
  61. Walz D. A., Wider M. D., Snow J. W., Dass C., and Desiderio D. M. (1988) The complete amino acid sequence of procine gastrotropin, an ileal protein which simulates gastricacid and pepsinogen secretion. J. Biol. Chem. 263, 14,189–14,195.Google Scholar
  62. Weisiger R. A. (1996) Cytoplasmic transport of lipids: role of binding proteins. Comp. Biochem. Physiol. 115B, 319–331.Google Scholar
  63. Xu L. Z., Sanchez R., Sali A., and Heintz N. (1996) Ligand specificity of brain lipid-binding protein. J. Biol. Chem. 271, 24,711–24,719.Google Scholar
  64. Young J. K., Baker J. H., and Müller T. (1996) Immunoreactivity for brain-fatty acid binding protein in Gomoripositive astrocytes. Glia 16, 218–226.PubMedCrossRefGoogle Scholar
  65. Zanotti G. (1999) Muscle fatty acid-binding protein. Biochim. Biophys. Acta 1441, 94–105.PubMedGoogle Scholar
  66. Zimmerman A. W. and Veerkamp J. H. (1998) Members of the fatty acid-binding protein family inhibit cell-free protein synthesis. FEBS Let. 437, 183–186.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity Medical Center St. RadboudNijmegenThe Netherlands

Personalised recommendations