Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA.
Adv Exp Med Biol. 2010;664:233-42. doi: 10.1007/978-1-4419-1399-9_27.
The disk membranes of retinal photoreceptor outer segments and other neuronal and reproductive tissues are enriched in docosahexaenoic acid (DHA, 22:6n3), which is essential for their normal function and development. The fatty acid condensing enzyme Elongation of Very Long chain fatty acids-4 (ELOVL4) is highly expressed in retina photoreceptors as well as other tissues with high 22:6n3 content. Mutations in the ELOVL4 gene are associated with autosomal dominant Stargardt-like macular dystrophy (STGD3) and results in synthesis of a truncated protein that cannot be targeted to the endoplasmic reticulum (ER), the site of fatty acid biosynthesis. Considering the abundance and essential roles of 22:6n3 in ELOVL4-expressing tissues (except the skin), it was proposed that the ELOVL4 protein may be involved in 22:6n3 biosynthesis. We tested the hypothesis that the ELOVL4 protein is involved in 22:6n3 biosynthesis by selectively silencing expression of the protein in the cone photoreceptors derived cell line 661 w and showed that the ELOVL4 protein is not involved in DHA biosynthesis from the short chain fatty acid precursors 18:3n3 and 22:5n3.
视网膜光感受器外段和其他神经元和生殖组织的盘膜富含二十二碳六烯酸(DHA,22:6n3),这对于它们的正常功能和发育是必不可少的。脂肪酸缩合酶长链脂肪酸延长酶 4(ELOVL4)在视网膜光感受器以及其他富含 22:6n3 的组织中高度表达。ELOVL4 基因突变与常染色体显性型 Stargardt 样黄斑营养不良(STGD3)相关,导致合成不能靶向内质网(ER)的截短蛋白,而 ER 是脂肪酸生物合成的部位。考虑到 ELOVL4 表达组织中 22:6n3 的丰富性和重要性(除皮肤外),有人提出 ELOVL4 蛋白可能参与 22:6n3 的生物合成。我们通过选择性沉默锥状光感受器衍生细胞系 661 w 中的 ELOVL4 蛋白表达来检验 ELOVL4 蛋白参与 22:6n3 生物合成的假说,并表明 ELOVL4 蛋白不参与从短链脂肪酸前体 18:3n3 和 22:5n3 合成 DHA。