RGD Reference Report - Protein mediated fatty acid uptake: synergy between CD36/FAT-facilitated transport and acyl-CoA synthetase-driven metabolism. - Rat Genome Database

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Protein mediated fatty acid uptake: synergy between CD36/FAT-facilitated transport and acyl-CoA synthetase-driven metabolism.

Authors: Schneider, Hannah  Staudacher, Sarah  Poppelreuther, Margarete  Stremmel, Wolfgang  Ehehalt, Robert  Füllekrug, Joachim 
Citation: Schneider H, etal., Arch Biochem Biophys. 2014 Mar 15;546:8-18. doi: 10.1016/j.abb.2014.01.025. Epub 2014 Feb 4.
RGD ID: 39458020
Pubmed: PMID:24503477   (View Abstract at PubMed)
DOI: DOI:10.1016/j.abb.2014.01.025   (Journal Full-text)

The mechanism of cellular fatty acid uptake is highly relevant for basic and clinical research. Previous work has demonstrated that fatty acid uptake is facilitated by cell surface membrane proteins as well as by intracellularly localized enzymes. Here, the exogenous expression of the CD36/FAT glycoprotein and the acyl-CoA synthetases FATP4 and ACSL1 in MDCK cells was quantified by comparison to recombinant proteins, and related to the corresponding increases of fatty acid uptake. At the molecular level, CD36/FAT was 30-fold more efficient than either FATP4 or ACSL1 in enhancing fatty acid uptake. Remarkably, co-expression of CD36/FAT with FATP4 or ACSL1 led to a higher increase of fatty acid uptake than expected from the combined individual contributions, whereas co-expression of FATP4 and ACSL1 did not. Immunofluorescence microscopy confirmed the plasma membrane localization of CD36/FAT and the intracellular localization of FATP4 to the endoplasmic reticulum, and of ACSL1 to mitochondria. Concluding, we suggest that fatty acid uptake in our model system is organized by two spatially distinct but synergistic mechanisms: the cell surface protein CD36/FAT directly facilitates fatty acid transport across the plasma membrane, whereas the intracellular acyl-CoA synthetases FATP4 and ACSL1 enhance fatty acid uptake indirectly by metabolic trapping.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Acsl1Ratpositive regulation of long-chain fatty acid import across plasma membrane involved_inIDA PMID:24503477ARUK-UCL 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Acsl1Ratmitochondrion located_inIDA PMID:24503477ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Acsl1  (acyl-CoA synthetase long-chain family member 1)


Additional Information