title: Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids.
abstract: Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile macular degeneration that eventually leads to loss of vision. Three independent mutations causing STGD3 have been identified in exon six of a gene named Elongation of very long chain fatty acids 4 (ELOVL4). The ELOVL4 protein was predicted to be involved in fatty acid elongation, although evidence for this and the specific step(s) it may catalyze have remained elusive. Here, using a gain-of-function approach, we provide direct and compelling evidence that ELOVL4 is required for the synthesis of C28 and C30 saturated fatty acids (VLC-FA) and of C28-C38 very long chain polyunsaturated fatty acids (VLC-PUFA), the latter being uniquely expressed in retina, sperm, and brain. Rat neonatal cardiomyocytes and a human retinal epithelium cell line (ARPE-19) were transduced with recombinant adenovirus type 5 carrying mouse Elovl4 and supplemented with 24:0, 20:5n3, or 22:5n3. The 24:0 was elongated to 28:0 and 30:0; 20:5n3 and 22:5n3 were elongated to a series of C28-C38 PUFA. Because retinal degeneration is the only known phenotype in STGD3 disease, we propose that reduced VLC-PUFA in the retinas of these patients may be the cause of photoreceptor cell death.
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
authors: Martin-Paul
authors: MP
authors: Agbaga
authors: Richard S
authors: RS
authors: Brush
authors: Md Nawajes A
authors: MN
authors: Mandal
authors: Kimberly
authors: K
authors: Henry
authors: Michael H
authors: MH
authors: Elliott
authors: Robert E
authors: RE
authors: Anderson
mesh_terms: D000818:Animals; D002460:Cell Line; D005136:Eye Proteins / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D019076:Transgenes
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins