Relationship of cholesterol content to spatial distribution and age of disc membranes in retinal rod outer segments.

Boesze‐Battaglia, Kathleen; Fliesler, Steven J.; Albert, Arlene D.

doi:10.1016/s0021-9258(17)30594-x

Cited by 72 publications

(6 citation statements)

References 35 publications

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“…[53][54][55][56] New discs are rich in cholesterol (∼30 mol% of total lipid, similar to the level of cholesterol in the plasma membrane), but become cholesterol-poor (∼5 mol%) as they mature along the outer segment. 57,58 Cholesterol inhibits rhodopsin activation and increases its stability: 54,56,59 thus rhodopsin in the plasma membrane and in new rod discs is relatively inactive in terms of phototransduction, and similarly may be inactive as a scramblase in these membranes. An interesting point is that in cone outer segments, discs are continuous with the plasma membrane 60 and therefore would be expected to be uniformly high in cholesterol.…”

Section: Mechanism Of Phospholipid Scramblingmentioning

confidence: 99%

Phospholipid scrambling by rhodopsin

Ernst

Menon

2015

Photochem Photobiol Sci

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Rhodopsin has been intensively characterized in its role as a visual pigment and G protein-coupled receptor responsible for dim-light vision. We recently discovered that it also functions as an ATP-independent phospholipid scramblase: when reconstituted into large unilamellar vesicles, rhodopsin accelerates the normally sluggish transbilayer translocation of common phospholipids by more than 1000-fold, to rates in excess of 10,000 phospholipids transported per rhodopsin per second. Here we summarize the work leading to this discovery and speculate on the mechanism by which rhodopsin scrambles phospholipids. We also present a hypothesis that rhodopsin’s scramblase activity is necessary for the function of the ABC transporter ABCA4 that is responsible for mitigating the toxic accumulation of 11-cis-retinal and bis-retinoids in the retina.

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Section: Mechanism Of Phospholipid Scramblingmentioning

confidence: 99%

Phospholipid scrambling by rhodopsin

Ernst

Menon

2015

Photochem Photobiol Sci

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“…Furthermore, the membranes contain on average about 10 mol % cholesterol (7). ROS membranes vary in cholesterol to phospholipid molar ratio from 0.30 to 0.05, with the higher cholesterol content in the basal, newly synthesized disks, and the lower cholesterol content at the apical tip (13,14). A large number of studies on cholesterol-phospholipid interaction have been conducted, but only a few general features of that interaction were established.…”

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confidence: 99%

Influence of Docosahexaenoic Acid and Cholesterol on Lateral Lipid Organization in Phospholipid Mixtures

1998

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We investigated lateral lipid organization in membranes with a lipid composition relevant to neural and retinal membranes [phosphatidylcholine (PC)/phosphatidylethanolamine (PE)/phosphatidylserine (PS)/cholesterol, 4/4/1/1, mol/mol/mol/mol]. The mixed-chain phospholipids contained saturated stearic acid (18:0) in the sn-1 position and the monounsaturated oleic acid (18:1) or polyunsaturated docosahexaenoic acid (22:6) in sn-2. Lateral lipid organization was evaluated by 2H NMR order parameter measurements on stearic acid of all individual types of phospholipids in the mixture and, through a novel approach, two-dimensional NOESY 1H NMR spectroscopy with magic angle spinning (MAS). The docosahexaenoic acid chain order was evaluated from 1H NMR chain signal MAS-sideband intensities. Averaged over all lipids, the cholesterol-induced increase in sn-1 chain order is 2-fold larger in monounsaturated than in polyunsaturated lipids, and the order of both saturated and polyunsaturated hydrocarbon chains increases. Addition of cholesterol increases lipid order in the sequence 18:0-18:1 PE > 18:0-18:1 PC > 18:0-18:1 PS for the monounsaturated and 18:0-22:6 PC >> 18:0-22:6 PE > 18:0-22:6 PS for polyunsaturated mixtures. The variation of order parameters between lipid species suggests that cholesterol induces the formation of lipid microdomains with a headgroup and chain unsaturation-dependent lipid composition. The preferential interaction between cholesterol and polyunsaturated 18:0-22:6 PC, followed by 18:0-22:6 PE and 18:0-22:6 PS, was confirmed by 1H MAS NOESY cross-relaxation rate differences. Furthermore, cholesterol preferentially associates with saturated chains in mixed-chain lipids reflected by higher saturated chain-to-cholesterol cross-relaxation rates. We propose that cholesterol forms PC-enriched microdomains in the polyunsaturated 18:0-22:6 PC/18:0-22:6 PE/18:0-22:6 PS/cholesterol membranes in which the saturated sn-1 chains are preferentially oriented toward the cholesterol molecules.

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“…According to the lipid composition of three types of membranes present in photoreceptor outer segments [ 5 , 6 , 7 ], liposomes with three different lipid compositions were prepared.…”

Section: Methodsmentioning

confidence: 99%

“…POS membranes are also enriched in phosphatidylethanolamines, in which mainly PUFAs are esterified [ 1 , 4 ]. The phospholipid composition and cholesterol content of subcellular components of photoreceptor outer segments enable to divide photoreceptor membranes into three types: plasma membranes (PM), young disc membranes (YDM), and old disc membranes (ODM) [ 5 , 6 , 7 ]. A high degree of lipid unsaturation [ 4 ], extended exposure to intensive irradiation [ 8 , 9 ], especially in the presence of endogenous sensitizers [ 10 ], and high respiratory demands [ 11 ] make these membranes sensitive to oxidative stress and lipid peroxidation [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Impact of Selected Retinoids on Model Photoreceptor Membranes

Radzin,

Wiśniewska-Becker,

Markiewicz

et al. 2023

Membranes

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Photoreceptor membranes have a unique lipid composition. They contain a high level of polyunsaturated fatty acids including the most unsaturated fatty acid in nature, docosahexaenoic acid (22:6), and are enriched in phosphatidylethanolamines. The phospholipid composition and cholesterol content of the subcellular components of photoreceptor outer segments enables to divide photoreceptor membranes into three types: plasma membranes, young disc membranes, and old disc membranes. A high degree of lipid unsaturation, extended exposure to intensive irradiation, and high respiratory demands make these membranes sensitive to oxidative stress and lipid peroxidation. Moreover, all-trans retinal (AtRAL), which is a photoreactive product of visual pigment bleaching, accumulates transiently inside these membranes, where its concentration may reach a phototoxic level. An elevated concentration of AtRAL leads to accelerated formation and accumulation of bisretinoid condensation products such as A2E or AtRAL dimers. However, a possible structural impact of these retinoids on the photoreceptor-membrane properties has not yet been studied. In this work we focused just on this aspect. The changes induced by retinoids, although noticeable, seem not to be significant enough to be physiologically relevant. This is, however, an positive conclusion because it can be assumed that accumulation of AtRAL in photoreceptor membranes will not affect the transduction of visual signals and will not disturb the interaction of proteins engaged in this process.

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Relationship of cholesterol content to spatial distribution and age of disc membranes in retinal rod outer segments.

Cited by 72 publications

References 35 publications

Phospholipid scrambling by rhodopsin

Phospholipid scrambling by rhodopsin

Influence of Docosahexaenoic Acid and Cholesterol on Lateral Lipid Organization in Phospholipid Mixtures

Structural Impact of Selected Retinoids on Model Photoreceptor Membranes

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