Diacylglycerol O-Acyltransferase Type-1 Synthesizes Retinyl Esters in the Retina and Retinal Pigment Epithelium

Kaylor, Joanna J.; Radu, Roxana A.; Bischoff, Nicholas; Makshanoff, Jacob; Hu, Jane; Lloyd, Monte; Eddington, Shannan; Bianconi, Tran; Bok, Dean; Travis, Gabriel H.

doi:10.1371/journal.pone.0125921

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…Although RPE expresses several a t RE synthases, the dominant enzyme is LRAT, which transfers the sn-1 palmitate of lecithin molecules to retinol [ 4 ]. Recent work has suggested that diacylglycerol O-acyltransferase-1 (DGAT1) can also synthesize a t RE in both the retina and RPE by acting as an acyl-CoA: retinol acyltransferase using palmitoyl-CoA as the acyl donor [ 30 ]. Together, LRAT and DGAT1 may exploit the increased FA uptake in hFATP1TG RPE to promote at RE synthesis.…”

Section: Discussionmentioning

confidence: 99%

Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina

et al. 2017

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In retinal pigment epithelium (RPE), RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1) is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice). The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40%) of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development.

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Section: Discussionmentioning

confidence: 99%

Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina

et al. 2017

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“…RPE65, an endoplasmic reticulum (ER)‐associated protein , is a key retinoid isomerase in the retinal pigment epithelium (RPE)‐dependent visual cycle that produces 11‐ cis‐ retinal . It catalyzes the synthesis of 11‐ cis ‐retinol from all‐ trans ‐retinyl fatty acid esters, such as all‐ trans ‐retinyl palmitate, synthesized by lecithin:retinol acyltransferase (LRAT) and other enzymes in the RPE . RPE65 is also the isomerase enzyme responsible for the production of meso ‐zeaxanthin, one of the three macular pigments that function as potent antioxidants and light screening pigments to protect macular from blue light damage and reactive oxygen species .…”

mentioning

confidence: 99%

Impacts of deletion and ichthyosis prematurity syndrome‐associated mutations in fatty acid transport protein 4 on the function of RPE65

Green

Jin

2019

FEBS Letters

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The retinal pigment epithelium‐specific 65 kDa (RPE65) isomerase plays a pivotal role in photoreceptor survival and function. RPE65‐catalyzed synthesis of 11‐cis‐retinol from all‐trans‐retinyl esters in the visual cycle is negatively regulated, through a heretofore unknown mechanism, by the fatty acid transport protein FATP4, mutations in which are associated with ichthyosis prematurity syndrome (IPS). Here, we analyzed the interaction between deletion mutants of FATP4 and RPE65 and the impacts of IPS‐associated FATP4 mutations on RPE65 expression, 11‐cis‐retinol synthesis, and all‐trans‐retinyl ester synthesis. Our results suggest that the interaction between FATP4 and RPE65 contributes to the inhibition of RPE65 function and that IPS‐associated nonsense and missense mutations in FATP4 have different effects on the visual cycle.

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“…The 11-cis-retinol thus formed can be stored as 11-cis-retinyl ester by action of the 11-cis ARAT. For this, two new 11-cis-specific retinyl ester synthases have been identified within the retina: the multifunctional O-acyltransferase (MFAT) (Kaylor et al 2014) and diacylglycerol O-acyltransferase-1 (DGAT1) 8 (Kaylor et al 2015), both found to be present in Müller glial cells and also in the GCL. In another series of studies, it was shown that primary embryonic cultures of Opn4x (+) RGCs were able to take up exogenous all-trans-retinal and isomerize it to 11-cis-retinal and other retinoids such as all-trans-retinol and all-trans-retinyl palmitate (Díaz et al 2017).…”

Section: The Visual Cycle In the Inner Retina And The Contribution Of Rgrmentioning

confidence: 99%

Non-visual Opsins and Novel Photo-Detectors in the Vertebrate Inner Retina Mediate Light Responses Within the Blue Spectrum Region

et al. 2020

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In recent decades, a number of novel non-visual opsin photopigments belonging to the family of G protein-coupled receptors, likely involved in a number of non-image-forming processes, have been identified and characterized in cells of the inner retina of vertebrates. It is now known that the vertebrate retina is composed of visual photoreceptor cones and rods responsible for diurnal/color and nocturnal/black and white vision, and cells like the intrinsically photosensitive retinal ganglion cells (ipRGCs) and photosensitive horizontal cells in the inner retina, both detecting blue light and expressing the photopigment melanopsin (Opn4). Remarkably, these non-visual photopigments can continue to operate even in the absence of vision under retinal degeneration. Moreover, inner retinal neurons and Müller glial cells have been shown to express other photopigments such as the photoisomerase retinal G protein-coupled receptor (RGR), encephalopsin (Opn3), and neuropsin (Opn5), all able to detect blue/violet light and implicated in chromophore recycling, retinal clock synchronization, neuronto-glia communication, and other activities. The discovery of these new photopigments in the inner retina of vertebrates is strong evidence of novel light-regulated activities. This review focuses on the features, localization, photocascade, and putative functions of these novel non-visual opsins in an attempt to shed light on their role in the inner retina of vertebrates and in the physiology of the whole organism.

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Diacylglycerol O-Acyltransferase Type-1 Synthesizes Retinyl Esters in the Retina and Retinal Pigment Epithelium

Cited by 11 publications

References 35 publications

Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina

Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina

Impacts of deletion and ichthyosis prematurity syndrome‐associated mutations in fatty acid transport protein 4 on the function of RPE65

Non-visual Opsins and Novel Photo-Detectors in the Vertebrate Inner Retina Mediate Light Responses Within the Blue Spectrum Region

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