The role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt macular degeneration.
ABCA4 is a member of the ABCA subfamily of ATP binding cassette (ABC) transporters that is expressed in rod and cone photoreceptors of the vertebrate retina. ABCA4, also known as the Rim protein and ABCR, is a large 2,273 amino acid glycoprotein organized as two tandem halves, each containing a single membrane spanning segment followed sequentially by a large exocytoplasmic domain, a multispanning membrane domain and a nucleotide binding domain. Over 500 mutations in the gene encoding ABCA4 are associated with a spectrum of related autosomal recessive retinal degenerative diseases including Stargardt macular degeneration, cone-rod dystrophy and a subset of retinitis pigmentosa. Biochemical studies on the purified ABCA4 together with analysis of abca4 knockout mice and patients with Stargardt disease have implicated ABCA4 as a retinylidene-phosphatidylethanolamine transporter that facilitates the removal of potentially reactive retinal derivatives from photoreceptors following photoexcitation. Knowledge of the genetic and molecular basis for ABCA4 related retinal degenerative diseases is being used to develop rationale therapeutic treatments for this set of disorders.
Molday
Robert S
RS
Department of Biochemistry, Centre for Macular Research, University of British Columbia, Vancouver, B.C., Canada V6T 1Z3. molday@interchange.ubc.ca
Zhong
Ming
M
Quazi
Faraz
F
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D006801:Humans; D050356:Lipid Metabolism; D008268:Macular Degeneration / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C512841:Abca4 protein, mouse