%0 Journal Article
%T Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains
%A Eric Soupene
%A Frans A Kuypers
%J BMC Molecular Biology
%D 2006
%I BioMed Central
%R 10.1186/1471-2199-7-21
%X Acyl-CoA Synthetase Long-chain member 6 (ACSL6) is responsible for activation of long-chain fatty acids in erythrocytes. Two additional transcript variants were also isolated from brain and testis. We report the expression in reticulocytes of two new variants and of the one isolated from brain. All three represented different spliced variants of a mutually exclusive exon pair. They encode a slightly different short motif which contains a conserved structural domain, the fatty acid Gate domain. The motifs differ in the presence of either the aromatic residue phenylalanine (Phe) or tyrosine (Tyr). Based on homology, two new isoforms for the closely related ACSL1 were predicted and characterized. One represented a switch of the Phe- to the Tyr-Gate domain motif, the other resulted from the exclusion of both. Swapping of this motif also appears to be common in all mammalian ACSL member 1 and 6 homologs.We propose that a Phe to Tyr substitution or deletion of the Gate domain, is the structural reason for the conserved alternative splicing that affects these motifs. Our findings support our hypothesis that this region is structurally important to define the activity of these enzymes.In mammals, long-chain acyl-CoA synthetases (ACSL) are necessary for fatty acid degradation, phospholipid remodeling, and production of long acyl-CoA esters that regulate various physiological processes. These enzymes play a crucial role in plasma membrane phospholipid turnover in erythrocytes, via the Lands pathway [1], as these cells lack the capacity for de novo lipid synthesis.In human, five ACSL genes have been identified with as many as 3 different transcript variants for each. The two recognized transcript variants for ACSL6 (formerly LACS5 [2]) were the only ones reported that represented spliced forms of a mutually exclusive pair of exons encoding a short highly conserved motif in the middle of the protein. All other variants differed in the amino terminus and/or the 5' UTR region. Wh
%U http://www.biomedcentral.com/1471-2199/7/21