Identification of a non-classical three-dimensional nuclear localization signal in the intestinal fatty acid binding protein

The intestinal fatty acid binding protein (FABP) is a small protein expressed along the small intestine that bind long-chain fatty acids and other hydrophobic ligands. Several lines of evidence suggest that, once in the nucleus, it interacts with nuclear receptors, activating them and thus transferring the bound ligand into the nucleus. Previous work by our group suggests that FABP2 would participate in the cytoplasm-nucleus translocation of fatty acids. Because the consensus NLS is absent in the sequence of FABP2, we propose that a 3D signal could be responsible for its nuclear translocation. The results obtained by transfection assays of recombinant wild type and mutated forms of Danio rerio Fabp2 in Caco-2 cell cultures, showed that lysine 17, arginine 29 and lysine 30 residues, which are located in the helix-turn-helix region, would constitute a functional non-classical three-dimensional NLS.

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Utilization of long chain fatty acids by rat liver: Studies of the role of fatty acid binding protein

Gastroenterology ◽

10.1016/0016-5085(79)90272-5 ◽

1979 ◽

Vol 77 (2) ◽

pp. 241-249 ◽

Cited By ~ 93

Author(s):

David A. Burnett ◽

Nina Lysenko ◽

Joan A. Manning ◽

Robert K. Ockner

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Rat Liver ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Long Chain Fatty Acids ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Long Chain

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Titration and Exchange Studies of Liver Fatty Acid-Binding Protein with13C-Labeled Long-Chain Fatty Acids†

Biochemistry ◽

10.1021/bi011914g ◽

2002 ◽

Vol 41 (17) ◽

pp. 5453-5461 ◽

Cited By ~ 16

Author(s):

Hsin Wang ◽

Yan He ◽

Christopher D. Kroenke ◽

Sarala Kodukula ◽

Judith Storch ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Long Chain Fatty Acids ◽

Liver Fatty Acid ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Long Chain ◽

Chain Fatty Acids

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Cytosolic fatty acid binding protein enhances rat hepatocyte [3H]palmitate uptake

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y99-087 ◽

1999 ◽

Vol 77 (11) ◽

pp. 896-901 ◽

Cited By ~ 12

Author(s):

F J Burczynski ◽

S Fandrey ◽

G Wang ◽

P A Pavletic ◽

Y Gong

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Long Chain Fatty Acids ◽

Clearance Rates ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Palmitate Uptake ◽

Long Chain

Liver cytosolic fatty acid binding protein (FABP) represents the intracellular equivalent to extracellular serum albumin, participating in the intracellular transport of long-chain fatty acids. In this study we observed the effect of increasing and decreasing FABP levels on hepatocyte [3H]palmitate uptake in male Sprague-Dawley rats. We also were interested to determine whether uptake, from either the unbound or unbound and protein-bound fractions, was fundamentally different at the different FABP levels. FABP levels were modified by hypophysectomy and clofibrate treatment (50 mg/100 g body weight for 10 days). Results showed that the [3H]palmitate clearance rates paralleled the 54% decrease and 73% increase in FABP levels in hypophysectomy and clofibrate-treated animals, respectively. In the presence of 2 and 20 µM albumin, hepatocyte clearance rates of unbound [3H]palmitate from hypophysectomized animals (0.16 ± 0.01 and 0.64 ± 0.01 mL·s-1·10-6 cells, respectively) were significantly lower (p < 0.01) than those of the sham group (0.30 ± 0.02 and 1.00 ± 0.06 mL·s-1·10-6 cells, respectively). However, the unbound [3H]palmitate clearance rates from the clofibrate-treated group (0.39 ± 0.04 and 1.18 ± 0.12 mL·s-1·10-6 cells) were significantly higher (p < 0.01) than the control group (0.29 ± 0.02 and 0.81 ± 0.05 mL·s-1·10-6 cells) for 2 and 20 µM albumin, respectively. To investigate whether uptake was fundamentally different between the hypophysectomized and clofibrate-treated groups, we expressed the clearance rates as enhancement factors, i.e., EF = CL20µM/CL2µM. No statistical difference was observed between EF of the hypophsectomized (3.8 ± 0.4) and EF of the clofibrate-treated (3.1 ± 0.3) groups, suggesting that the extracted ligand originated from similar fractions.Key words: palmitic acid, albumin, growth hormone, liver, fatty acid binding protein, uptake, hepatic, long-chain fatty acids, clofibrate, hypophysectomy.

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Rat intestinal fatty acid binding protein. A model system for analyzing the forces that can bind fatty acids to proteins.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)46634-8 ◽

1993 ◽

Vol 268 (25) ◽

pp. 18399-18402 ◽

Cited By ~ 2

Author(s):

J.C. Sacchettini ◽

J.I. Gordon

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Protein A ◽

Model System ◽

Fatty Acid Binding ◽

Acid Binding Protein

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Up-regulation of the expression of the gene for liver fatty acid-binding protein by long-chain fatty acids

Biochemical Journal ◽

10.1042/bj3190483 ◽

1996 ◽

Vol 319 (2) ◽

pp. 483-487 ◽

Cited By ~ 47

Author(s):

Claire MEUNIER-DURMORT ◽

Hélène POIRIER ◽

Isabelle NIOT ◽

Claude FOREST ◽

Philippe BESNARD

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Fold Increase ◽

Long Chain Fatty Acids ◽

Liver Fatty Acid ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Fabp Gene ◽

Long Chain

The role of fatty acids in the expression of the gene for liver fatty acid-binding protein (L-FABP) was investigated in the well-differentiated FAO rat hepatoma cell line. Cells were maintained in serum-free medium containing 40 µM BSA/320 µM oleate. Western blot analysis showed that oleate triggered an approx. 4-fold increase in the cytosolic L-FABP level in 16 h. Oleate specifically stimulated L-FABP mRNA in time-dependent and dose-dependent manners with a maximum 7-fold increase at 16 h in FAO cells. Preincubation of FAO cells with cycloheximide prevented the oleate-mediated induction of L-FABP mRNA, showing that protein synthesis was required for the action of fatty acids. Run-on transcription assays demonstrated that the control of L-FABP gene expression by oleate was, at least in part, transcriptional. Palmitic acid, oleic acid, linoleic acid, linolenic acid and arachidonic acid were similarly potent whereas octanoic acid was inefficient. This regulation was also found in normal hepatocytes. Therefore long-chain fatty acids are strong inducers of L-FABP gene expression. FAO cells constitute a useful tool for studying the underlying mechanism of fatty acid action.

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The integrity of the α-helical domain of intestinal fatty acid binding protein is essential for the collision-mediated transfer of fatty acids to phospholipid membranes

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2008.01.005 ◽

2008 ◽

Vol 1781 (4) ◽

pp. 192-199 ◽

Cited By ~ 15

Author(s):

G.R. Franchini ◽

J. Storch ◽

B. Corsico

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Phospholipid Membranes ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Helical Domain

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Inhibition of binding to fatty acid binding protein reduces the intracellular transport of fatty acids

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1996.271.1.g113 ◽

1996 ◽

Vol 271 (1) ◽

pp. G113-G120 ◽

Cited By ~ 4

Author(s):

B. A. Luxon

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Intracellular Transport ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Female Rats ◽

Dependent Manner ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Cytoplasmic Transport

Male livers, containing lesser amounts of fatty acid binding protein (FABP), utilize fatty acids more slowly than female livers. Conventional wisdom dictates that FABP stimulates fatty acid use by increasing cytoplasmic transport rates. Previously, we showed that the cytoplasmic diffusion of a fatty acid analogue [12-N-methyl-7-nitrobenzo-2-oxa-1,3-diazol-amino stearate (NBD-stearate)] is faster in female hepatocytes, paralleling the larger amounts of FABP. Sex differences in other cytoplasmic factors could also lead to faster diffusion, independent of FABP levels. The aim of this study was to determine the effect of inhibition of fatty acid binding to FABP on the directly measured intracellular transport rate of NBD-stearate. The binding of NBD-stearate to FABP was reduced by incubating hepatocytes isolated from male and female rats with alpha-bromo-palmitate (0-1,500 microM), a modified long-chain fatty acid that binds to FABP. The inhibition by alpha-bromo-palmitate on NBD-stearate binding to FABP was measured with the use of centrifugation to separate cytosol from cytoplasmic membranes. Laser photobleaching (fluorescence recovery after photobleaching) was used to measure the cytoplasmic diffusion of NBD-stearate in hepatocytes. Alpha-Bromo-palmitate incubation reduced NBD-stearate binding to FABP in a dose-dependent manner. The measured diffusion rate was also reduced in proportion to the degree of binding inhibition. We conclude that cytoplasmic transport of NBD-stearate is modulated by binding to soluble proteins like FABP. FABP enhances diffusive transport by reducing binding to immobile cytosolic membranes.

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