Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids.

Proceedings of the National Academy of Sciences of the United States of America
Martin-Paul AgbagaRobert E Anderson

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.

References

Jan 1, 1988·The Biochemical Journal·N P Rotstein, M I Aveldaño
Jan 1, 1983·Progress in Lipid Research·S J Fliesler, R E Anderson
Jun 15, 1996·The Biochemical Journal·N P RotsteinM I Aveldaño
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·Z B KangJ X Kang
Jun 26, 2003·Investigative Ophthalmology & Visual Science·Pamela S LagaliRadha Ayyagari
Oct 29, 2003·The Journal of Biological Chemistry·Rolf WesterbergAnders Jacobsson
Nov 26, 2003·Progress in Lipid Research·Amanda E LeonardYung-Sheng Huang
Apr 14, 2004·Archives of Ophthalmology·Marco A Zarbin
Mar 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·G KaranK Zhang
Mar 26, 2005·Investigative Ophthalmology & Visual Science·Rex E MartinRobert E Anderson
Jul 23, 2005·The Journal of Biological Chemistry·Celene Grayson, Robert S Molday
Sep 28, 2005·Investigative Ophthalmology & Visual Science·Jingnan Xiao, James Chodosh
Dec 6, 2005·The Journal of Biological Chemistry·Rolf WesterbergAnders Jacobsson
Mar 25, 2006·Science·Jean Marx
Mar 28, 2006·Progress in Lipid Research·Andreas JakobssonAnders Jacobsson
Aug 1, 2006·Investigative Ophthalmology & Visual Science·Dorit Raz-PragPaul A Sieving
Sep 28, 2006·Investigative Ophthalmology & Visual Science·Vidyullatha VasireddyRadha Ayyagari
Feb 17, 2007·International Journal of Biological Sciences·D Joshua CameronKang Zhang
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Thomas ChertempsClaude Wicker-Thomas
Mar 30, 2007·The Journal of Biological Chemistry·Natalia E FurlandMarta I Aveldaño
Aug 28, 2007·Cell·Vladimir Denic, Jonathan S Weissman

❮ Previous
Next ❯

Citations

Jan 14, 2012·Journal of the American Chemical Society·Stephan H von ReussFrank C Schroeder
Mar 10, 2010·Nature Reviews. Genetics·Alan F WrightShomi S Bhattacharya
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·James S FriedmanAnand Swaroop
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Peter BarabasDavid Križaj
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sreemathi LoganRobert E Anderson
Dec 27, 2011·The Journal of Biological Chemistry·Richard HarkewiczKang Zhang
Mar 28, 2012·The Journal of Biological Chemistry·Xiaoman LiMichael H Elliott
Feb 25, 2010·Human Molecular Genetics·Stéphane FourcadeAurora Pujol
Dec 14, 2011·Journal of Lipid Research·Man YuMartin-Paul Agbaga
Aug 12, 2009·Journal of Lipid Research·Janet R SparrowJilin Zhou
Mar 20, 2010·Journal of Lipid Research·Martin-Paul AgbagaRobert E Anderson
Jan 29, 2013·WormBook : the Online Review of C. Elegans Biology·Andreas H Ludewig, Frank C Schroeder
Dec 24, 2013·Progress in Lipid Research·Manabu T NakamuraJuan J Loor
May 7, 2013·Clinical Lipidology·Julia V BusikGavin E Reid
Apr 8, 2011·Annual Review of Biochemistry·Richard Harkewicz, Edward A Dennis
Aug 31, 2013·Biochimica Et Biophysica Acta·Mariona RabionetRoger Sandhoff
Mar 19, 2013·Experimental Eye Research·Alejandro GarantoRoser Gonzàlez-Duarte
Jan 3, 2012·Progress in Retinal and Eye Research·Janet R SparrowJilin Zhou
Mar 8, 2011·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Greta Carmona-AntoñanzasDouglas R Tocher
Jul 17, 2010·Progress in Lipid Research·Robert S Molday, Kang Zhang
Jan 26, 2010·Progress in Retinal and Eye Research·Vidyullatha VasireddyRadha Ayyagari
Sep 22, 2015·The Journal of Pathology·Corinne Kostic, Yvan Arsenijevic
Dec 19, 2009·Progress in Lipid Research·Hervé GuillouAnders Jacobsson
Oct 27, 2009·Experimental Eye Research·Matthew BedellKang Zhang
Apr 29, 2009·Progress in Retinal and Eye Research·Alan D MarmorsteinNeal S Peachey
Jul 16, 2010·Brain Pathology·Stephan Kemp, Ronald Wanders
Feb 10, 2016·Scientific Reports·Óscar MonroigL Filipe C Castro

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.