Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina
Open accessAbstract
Absorption of a light particle by an opsin-pigment causes photoisomerization of its retinaldehyde chromophore. Restoration of light sensitivity to the resulting apo-opsin requires chemical re-isomerization of the photobleached chromophore. This is carried out by a multistep enzyme pathway called the visual cycle. Accumulating evidence suggests the existence of an alternative visual cycle for regenerating opsins in daylight. Here we identified dihydroceramide desaturase-1 (DES1) as a retinol isomerase and an excellent candidate for isomerase-2 in this alternative pathway. DES1 is expressed in retinal Müller cells, where it coimmunoprecipitates with cellular retinaldehyde binding protein (CRALBP). Adenoviral gene therapy with DES1 partially rescued the biochemical and physiological phenotypes in Rpe65(-/-) mice lacking isomerohydrolase (isomerase-1). Knockdown of DES1 expression by RNA interference concordantly reduced isomerase-2 activity in cultured Müller cells. Purified DES1 had very high isomerase-2 activity in the presence of appropriate cofactors, suggesting that DES1 by itself is sufficient for isomerase activity.
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Because rods depend entirely on 11-cis-retinal and cones can also utilize 11-cis-retinol, competition for this visual cycle product is avoided.
“As rods depend entirely on 11-cis-retinal and cones can also utilize 11-cis-retinol, the competition for this visual cycle product is avoided [52,63,65,66].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [63]
The Discussion says cones, but not rods, can use 11-cis-retinol to recover photosensitivity, and that cones can escape competition with rods by taking up 11-cis-retinol as a chromophore precursor. But it also describes rods using 9-cis-retinal, so the claim that rods depend entirely on 11-cis-retinal is too absolute. Page numbers are not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDES-1 produces mainly 9-cis- and 13-cis-retinoids rather than 11-cis-retinoids from all-trans-retinol, which is unexpected given the abundance of 11-cis-retinoids in chicken retina.
“DES-1 produces mainly 9-cis- and 13-cis-retinoids rather than 11-cis-retinoids from all-trans-retinol, which is unexpected given the abundance of 11-cis-retinoids in the chicken retina.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [308]
DES-1 was identified as a candidate protein for the alternative retinoid isomerization activity found in chicken retinas.
“A candidate protein responsible for the alternative retinoid isomerization (all-trans-retinol to 11-cis-retinol) activity found in chicken retinas was identified as dihydroceramide desaturase-1 (DES-1)”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [308]
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References 53 · Cited by 107
- Authors
- Kaylor, J. J., Yuan, Q., Cook, J., Sarfare, S., Makshanoff, J., Miu, A., Kim, A., Kim, P., Habib, S., Roybal, C. N., Xu, T., Nusinowitz, S., & Travis, G. H.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Travis, Gabriel H
- Venue
- Nature Chemical Biology
- Published
- 2012-11-11
- Volume
- 9
- Issue
- 1
- Pages
- 30-36
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3522777
- OpenAlex
- W2071256547
- Cited by
- 107
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 12 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 17 · 2014: 11 · 2013: 11 · 2012: 2
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Eye Institute (R01-EY11713, R01EY011713, P30EY000331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- Müller cells, retina, visual cycle, CRALBP, RPE65, retinal, photoreceptors, gene therapy
- MeSH terms
- Retinoid Isomerohydrolase, Dependovirus, Animals, Chickens, Genetic Vectors, Isomerases, Isomerism, Neuroglia, Oxidoreductases, Retina, Vitamin A, Genetic Therapy, Mice, Knockout, cis-trans-Isomerases, Mice
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