Focus on Molecules: ABCA4 (ABCR) – An import-directed photoreceptor retinoid flipase

Sullivan, Jack

doi:10.1016/j.exer.2009.03.005

Cited by 17 publications

(18 citation statements)

References 4 publications

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“…Retinae of both the Rdh8 À/À /Abca4 À/À16 (Figs. 4,5) and Crb1 rd8 /Crb1 rd8 mutant mice 19 are described as having photoreceptor cell rosettes. Interestingly, patients with retinal degeneration due to CRB1 mutations also exhibit intraretinal hyperreflective lesions that the authors suggest could represent the rosettes observed in mice.…”

Section: Discussionmentioning

confidence: 99%

Fundus Autofluorescence and Photoreceptor Cell Rosettes in Mouse Models

Flynn

Ueda

Auran

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 99%

Fundus Autofluorescence and Photoreceptor Cell Rosettes in Mouse Models

Flynn

Ueda

Auran

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…Furthermore, a solid phase assay revealed that the ratio between the bound N -retinylidene-PE and ABCA4 is approximately 1:1 and, most importantly, that ATP could release N -retinylidene-PE and all- trans -retinal from the protein, while ADP and AMP-PNP were far less effective in this regard (Beharry et al 2004). Based on these studies, it has been accepted that biochemical evidence points to retinal and N -retinylidene-PE as transported substrates of ABCA4 (Molday 2007; Molday et al 2009; Sullivan 2009; Vasiliou et al 2009). Of note, both the basal and the stimulated ATPase activities of ABCA4 varied significantly from study to study and among protein preparations, displaying a strong dependence on detergent type, the presence and composition of lipids and the presence of a reducing agent among other factors (Ahn et al 2000; Sun et al 1999).…”

Section: Biological Role Of Abca4mentioning

confidence: 99%

“…Several working models of transport have been suggested for ABCA4 that mostly differ with respect to the roles of NBDs, as described above (Molday 2007; Molday et al 2009; Sullivan 2009; Sun et al 2000). The proposed mechanism of transport is based on the ‘alternating access’ model, established for smaller ABC transporters (Kos and Ford 2009; Linton and Higgins 2007; Rees et al 2009).…”

Section: Biological Role Of Abca4mentioning

confidence: 99%

The ATP-Binding Cassette Transporter ABCA4: Structural and Functional Properties and Role in Retinal Disease

Tsybovsky

Molday²,

Palczewski³

2010

Advances in Experimental Medicine and Biology

160

154

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ATP-binding cassette transporters (ABC transporters) utilize the energy of ATP hydrolysis to translocate an unusually diverse set of substrates across cellular membranes. ABCA4, also known as ABCR, is a ~250 kDa single-chain ABC transporter localized to the disk margins of vertebrate photoreceptor outer segments. It is composed of two symmetrically organized halves, each comprising six membrane-spanning helices, a large glycosylated exocytoplasmic domain located inside the disk, and a cytoplasmic domain with an ATP-binding cassette. Hundreds of mutations in ABCA4 are known to cause impaired vision and blindness such as in Stargardt disease as well as related disorders. Biochemical and animal model studies in combination with patient analyses suggest that the natural substrate of ABCA4 is retinylidene-phosphatidylethanolamine (N-retinylidene-PE), a precursor of potentially toxic diretinal compounds. ABCA4 prevents accumulation of N-retinylidene-PE inside the disks by transporting it to the cytoplasmic side of the disk membrane where it can dissociate, allowing the released all-trans-retinal to enter the visual cycle. The pathogenesis of diseases caused by mutations in ABCA4 is complex, comprising a loss-of-function component as well as photoreceptor stress caused by protein mislocalization and misfolding.

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“…In the rod photoreceptor, due to complete invagination of the outer segment plasma membranes to form topologically closed disks that stack inside an embracing surface plasma membrane, most of the ABCR becomes localized to the edges of internalized disk membranes; a residual fraction of ABCR is expressed to the surface plasma membrane of the outer segment that envelopes the stack of disks. ABCR is known as a retinoid flipase and uses the energy from ATP breakdown to catalyze the transmembrane transfer of ATR-derived molecules in the photoreceptor outer segments [56]. The net vector of retinoid movement is from the outside surface of the visual pigment containing membranes to the inside (cytoplasmic) surfaces.…”

Section: Abcrmentioning

confidence: 99%