Retinal-phospholipid Schiff-base conjugates and their interaction with ABCA4, the ABC transporter associated with Stargardt disease

Xu, Tongzhou; Molday, LaurieL.; Molday, Robert S.

doi:10.1016/j.jbc.2023.104614

Cited by 6 publications

(3 citation statements)

References 57 publications

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“…For example, newly synthesized GPCRs may contribute to the biogenic function of the endoplasmic reticulum, a membrane with just ∼5% cholesterol ( 7 , 20 , 62 , 63 ), by scrambling phospholipids to promote membrane bilayer assembly ( 64 , 65 , 66 , 67 ). Third, the cholesterol concentration in bovine rod outer segment disks which house rhodopsin is low, ∼10% ( 68 ), suggesting that opsin-mediated phospholipid scrambling in disks occurs constitutively ( 69 , 70 , 71 ) to offset the bilayer disrupting activities of ATP-driven transporters ( 4 , 72 ).…”

Section: Discussionmentioning

confidence: 99%

A cholesterol switch controls phospholipid scrambling by G protein–coupled receptors

Menon,

Sych,

Son

et al. 2024

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

A cholesterol switch controls phospholipid scrambling by G protein–coupled receptors

Menon,

Sych,

Son

et al. 2024

Journal of Biological Chemistry

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“…For example, newly synthesized GPCRs may contribute to the biogenic function of the endoplasmic reticulum, a membrane with just ~5% cholesterol (7,20,60,61), by scrambling phospholipids to promote membrane bilayer assembly (62)(63)(64)(65). The cholesterol concentration in bovine rod outer segment disks which house rhodopsin is also low, ~10% (66), suggesting that opsin-mediated phospholipid scrambling in disks occurs constitutively (67-69) to offset the bilayer disrupting activities of ATP-driven transporters (4,70).…”

Section: Discussionmentioning

confidence: 99%

A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors

Menon,

Sych,

Son

et al. 2023

Preprint

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Class A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma membrane of metazoan cells is replete with GPCRs, yet has a strong resting trans-bilayer phospholipid asymmetry, with the signaling lipid phosphatidylserine confined to the cytoplasmic leaflet. To account for the persistence of this lipid asymmetry in the presence of GPCR scramblases, we hypothesized that GPCR-mediated lipid scrambling is regulated by cholesterol, a major constituent of the plasma membrane. We now present a technique whereby synthetic vesicles reconstituted with GPCRs can be supplemented with cholesterol to a level similar to that of the plasma membrane and show that the scramblase activity of two prototypical GPCRs, opsin and the β1-adrenergic receptor, is impaired upon cholesterol loading. Our data suggest that cholesterol acts as a switch, inhibiting scrambling above a receptor-specific threshold concentration to disable GPCR scramblases at the plasma membrane.

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“…Additionally, i PrOH/NaBH 4 also trapped retinal that subsequently went on to form Schiff base adducts with membrane‐derived phosphatidylethanolamines (PE). [ 108 ] These PE‐adducts were identified from LC‐MS/MS analysis of the lipid soluble fraction and were found to form at a rate that was an order of magnitude faster than that of their hydrolysis from Rho*, as measured in isolation by the addition of exogenous all‐ trans ‐retinal to ROS membranes (Figure 5G). [ 61 ] Notably, the LC‐MS/MS based method described above does not directly measure the kinetics of the release of all‐ trans ‐retinal from the chromophore binding pocket after Rho* hydrolysis.…”

Section: Lc‐ms/ms‐based Methods Of Tracking Rho* Decaymentioning

confidence: 99%

A short story on how chromophore is hydrolyzed from rhodopsin for recycling

Hong

Palczewski

2023

BioEssays

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The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and Kühne in the 1870s inspired over a century's worth of investigations on rhodopsin biochemistry. A single photon isomerizes the Schiff‐base linked 11‐cis‐retinylidene chromophore of rhodopsin, converting it to the all‐trans agonist to elicit phototransduction through photoactivated rhodopsin (Rho*). Schiff base hydrolysis of the agonist is a key step in the photocycle, not only diminishing ongoing phototransduction but also allowing for entry and binding of fresh 11‐cis chromophore to regenerate the rhodopsin pigment and maintain light sensitivity. Many challenges have been encountered in measuring the rate of this hydrolysis, but recent advancements have facilitated studies of the hydrolysis within the native membrane environment of rhodopsin. These techniques can now be applied to study hydrolysis of agonist in other opsin proteins that mediate phototransduction or chromophore turnover. In this review, we discuss the progress that has been made in characterizing the rhodopsin photocycle and the journey to characterize the hydrolysis of its all‐trans‐retinylidene agonist.

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Retinal-phospholipid Schiff-base conjugates and their interaction with ABCA4, the ABC transporter associated with Stargardt disease

Cited by 6 publications

References 57 publications

A cholesterol switch controls phospholipid scrambling by G protein–coupled receptors

A cholesterol switch controls phospholipid scrambling by G protein–coupled receptors

A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors

A short story on how chromophore is hydrolyzed from rhodopsin for recycling

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