High impact information on FABP4

• Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals [1].
• We propose that phosphorylation of the AP2 mu 2 subunit by AAK1 ensures high affinity binding of AP2 to sorting signals of cargo membrane proteins during the initial steps of receptor-mediated endocytosis [1].
• Mechanism of interaction between leucine-based sorting signals from the invariant chain and clathrin-associated adaptor protein complexes AP1 and AP2 [2].
• AP1 and AP2 both bind to and dissociate from the MPR46 tail with similar kinetics [3].
• Fatty acid bing protein 4 (FABP4) plays a key role in fat regulation in mammals and is a strong positional candidate gene for the FAT1 quantitative trait locus located on porcine chromosome 4 [4].

Biological context of FABP4

• The A-FABP gene was assigned to porcine Chromosome (Chr) 4 by a porcine sequence-specific PCR on a cell hybrid panel, fully consistent with comparative mapping data with human and mouse [5].
• This genetic variation within the A-FABP gene was associated with differences in IMF content and possibly growth in a Duroc population, whereas no effect on backfat thickness and drip loss of the meat were detected [5].
• In the first intron of the porcine A-FABP gene, a microsatellite sequence was detected that was polymorphic for all six pig breeds tested [5].
• Within this region, a 56-bp nucleotide sequence was completely identical with the corresponding sequence in the mouse A-FABP gene, which contains the transcription factor binding sites for C/EBP and AP-1, and is implicated in the differentiation-dependent regulation of A-FABP [5].
• Also strikingly, the FABP4 phylogenetic tree did not show any geographical or breed origin clustering, with distant breeds sharing similar haplotypes and some of the most heterozygous samples pertaining to highly inbred animals like Iberian Guadyerbas (inbreeding coefficient approximately 0.3) or British Tamworth [4].

Anatomical context of FABP4

• Addition of TTNPB decreased (P < 0.001) the expression of peroxisome proliferator-activated receptor gamma (PPARgamma), sterol regulatory element-binding protein-1c (SREBP-1c), retinoid X receptor alpha (RXRalpha), and adipocyte fatty acid binding protein (aP2) mRNA transcripts, whereas these effects were prevented by the presence of Ro-61 [6].
• According to linkage and RH mapping, this gene is located close to the FABP4 (fatty acid binding protein 4, adipocyte) gene on swine chromosome 4 [7].
• Requirement for proximal putative Sp1 and AP-2 cis-deoxyribonucleic acid elements in mediating basal and luteinizing hormone- and insulin-dependent in vitro transcriptional activation of the CYP17 gene in porcine theca cells [8].
• The increased expression of PPARgamma and AFABP indicates that CLA induced the development of preadipocytes from stromal-vascular (s-v) stem cells to promote intramuscular fat content [9].

Associations of FABP4 with chemical compounds

• Phosphorylation of mu 2 occurs at a single threonine residue (Thr-156) and is mediated by the newly discovered adaptor-associated kinase, AAK1, which copurifies with AP2 [1].
• Immunofluorescence demonstrated that the Na/K-ATPase colocalized with clathrin both before and after exposure to ouabain, and immunoprecipitation experiments confirmed that ouabain stimulated interactions among the Na/K-ATPase, adaptor protein-2 (AP-2), and clathrin [10].
• Depletion of cholesterol also significantly reduced the protein-protein interaction among alpha-1 subunit, AP2, PI-3K, and clathrin heavy chain [11].
• A series of assay procedures, combining the AP2 test (adjuvant and 24-h occlusive patch 2x test, as previously reported) with intraperitoneal cyclophosphamide administration, were examined [12].

Other interactions of FABP4

• Previously, polymorphisms in the adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, have been significantly associated with genetic variation of intramuscular fat content in a Duroc pig population [13].
• In contrast to previous findings for Duroc pigs, no evidence was found for an effect of the A-FABP gene on IMF or BFT in this population [14].

References