Publications

• Comparative biochemical studies of the murine fatty acid transport proteins (FATP) expressed in yeast.

  DiRusso C.C., Li H., Darwis D., Watkins P.A., Berger J., Black P.N.

  The fatty acid transport protein (FATP) family is a group of proteins that are predicted to be components of specific fatty acid trafficking pathways. In mammalian systems, six different isoforms have been identified, which function in the import of exogenous fatty acids or in the activation of ve ... >> More

  The fatty acid transport protein (FATP) family is a group of proteins that are predicted to be components of specific fatty acid trafficking pathways. In mammalian systems, six different isoforms have been identified, which function in the import of exogenous fatty acids or in the activation of very long-chain fatty acids. This has led to controversy as to whether these proteins function as membrane-bound fatty acid transporters or as acyl-CoA synthetases, which activate long-chain fatty acids concomitant with transport. The yeast FATP orthologue, Fat1p, is a dual functional protein and is required for both the import of long-chain fatty acids and the activation of very long-chain fatty acids; these activities intrinsic to Fat1p are separable functions. To more precisely define the roles of the different mammalian isoforms in fatty acid trafficking, the six murine proteins (mmFATP1-6) were expressed and characterized in a genetically defined yeast strain, which cannot transport long-chain fatty acids and has reduced long-chain acyl-CoA synthetase activity (fat1Delta faa1Delta). Each isoform was evaluated for fatty acid transport, fatty acid activation (using C18:1, C20:4, and C24:0 as substrates), and accumulation of very long-chain fatty acids. Murine FATP1, -2, and -4 complemented the defects in fatty acid transport and very long-chain fatty acid activation associated with a deletion of the yeast FAT1 gene; mmFATP3, -5, and -6 did not complement the transport function even though each was localized to the yeast plasma membrane. Both mmFATP3 and -6 activated C20:4 and C20:4, while the expression of mmFATP5 did not substantially increase acyl-CoA synthetases activities using the substrates tested. These data support the conclusion that the different mmFATP isoforms play unique roles in fatty acid trafficking, including the transport of exogenous long-chain fatty acids. << Less

  J. Biol. Chem. 280:16829-16837(2005) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Oligomerization of the murine fatty acid transport protein 1.

  Richards M.R., Listenberger L.L., Kelly A.A., Lewis S.E., Ory D.S., Schaffer J.E.

  The 63-kDa murine fatty acid transport protein 1 (FATP1) was cloned on the basis of its ability to augment fatty acid import when overexpressed in mammalian cells. The membrane topology of this integral plasma membrane protein does not resemble that of polytopic membrane transporters for other sub ... >> More

  The 63-kDa murine fatty acid transport protein 1 (FATP1) was cloned on the basis of its ability to augment fatty acid import when overexpressed in mammalian cells. The membrane topology of this integral plasma membrane protein does not resemble that of polytopic membrane transporters for other substrates. Western blot analysis of 3T3-L1 adipocytes that natively express FATP1 demonstrate a prominent 130-kDa species as well as the expected 63-kDa FATP1, suggesting that this protein may participate in a cell surface transport protein complex. To test whether FATP1 is capable of oligomerization, we expressed functional FATP1 molecules with different amino- or carboxyl-terminal epitope tags in fibroblasts. These epitope-tagged proteins also form apparent higher molecular weight species. We show that, when expressed in the same cells, differentially tagged FATP1 proteins co-immunoprecipitate. The region between amino acid residues 191 and 475 is sufficient for association of differentially tagged truncated FATP1 constructs. When wild type FATP1 and the non-functional s250a FATP1 mutant are co-expressed in COS7 cells, mutant FATP1 has dominant inhibitory function in fatty acid uptake assays. Taken together, these results are consistent with a model in which FATP1 homodimeric complexes play an important role in cellular fatty acid import. << Less

  J. Biol. Chem. 278:10477-10483(2003) [PubMed] [EuropePMC]

• Molecular aspects of fatty acid transport: mutations in the IYTSGTTGXPK motif impair fatty acid transport protein function.

  Stuhlsatz-Krouper S.M., Bennett N.E., Schaffer J.E.

  The murine fatty acid transport protein (FATP) facilitates uptake of long chain fatty acids (LCFAs) when expressed in mammalian cells. FATP's sequence contains a highly conserved motif, IYTSGTTGXPK, also found in a number of proteins known to interact with ATP. To explore the role of this motif, w ... >> More

  The murine fatty acid transport protein (FATP) facilitates uptake of long chain fatty acids (LCFAs) when expressed in mammalian cells. FATP's sequence contains a highly conserved motif, IYTSGTTGXPK, also found in a number of proteins known to interact with ATP. To explore the role of this motif, we independently mutated the central serine (serine 250) and threonine (threonine 252) residues in this motif and assessed the effects of these mutations on FATP function. When expressed in fibroblasts, the FATP mutants demonstrated impaired LCFA import and impaired binding of [alpha-32P]8-azido-ATP (azido-ATP) compared with wild-type FATP. These results suggest that serine 250 and threonine 252 are critical for FATP function and that the mechanism of action of FATP involves nucleotide binding which is dependent on these residues. << Less

  Prostaglandins Leukot. Essent. Fatty Acids 60:285-289(1999) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.