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RDH12 allows cone photoreceptors to regenerate opsin visual pigments from a chromophore precursor to escape competition with rods.
Kaylor, Joanna J; Frederiksen, Rikard; Bedrosian, Christina K; Huang, Melody; Stennis-Weatherspoon, David; Huynh, Theodore; Ngan, Tiffany; Mulamreddy, Varsha; Sampath, Alapakkam P; Fain, Gordon L; Travis, Gabriel H.
Afiliación
  • Kaylor JJ; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Frederiksen R; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Bedrosian CK; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Huang M; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Stennis-Weatherspoon D; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Huynh T; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Ngan T; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Mulamreddy V; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Sampath AP; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Fain GL; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
  • Travis GH; University of California, Los Angeles, David Geffen School of Medicine, Department of Ophthalmology, 405 Hilgard Avenue, Los Angeles, CA 90095, USA; University of California Los Angeles, Department of Biological Chemistry, 405 Hilgard Avenue, Los Angeles, CA 90095, USA. Electronic address: travis@js
Curr Biol ; 34(15): 3342-3353.e6, 2024 Aug 05.
Article en En | MEDLINE | ID: mdl-38981477
ABSTRACT
Capture of a photon by an opsin visual pigment isomerizes its 11-cis-retinaldehyde (11cRAL) chromophore to all-trans-retinaldehyde (atRAL), which subsequently dissociates. To restore light sensitivity, the unliganded apo-opsin combines with another 11cRAL to make a new visual pigment. Two enzyme pathways supply chromophore to photoreceptors. The canonical visual cycle in retinal pigment epithelial cells supplies 11cRAL at low rates. The photic visual cycle in Müller cells supplies cones with 11-cis-retinol (11cROL) chromophore precursor at high rates. Although rods can only use 11cRAL to regenerate rhodopsin, cones can use 11cRAL or 11cROL to regenerate cone visual pigments. We performed a screen in zebrafish retinas and identified ZCRDH as a candidate for the enzyme that converts 11cROL to 11cRAL in cone inner segments. Retinoid analysis of eyes from Zcrdh-mutant zebrafish showed reduced 11cRAL and increased 11cROL levels, suggesting impaired conversion of 11cROL to 11cRAL. By microspectrophotometry, isolated Zcrdh-mutant cones lost the capacity to regenerate visual pigments from 11cROL. ZCRDH therefore possesses all predicted properties of the cone 11cROL dehydrogenase. The human protein most similar to ZCRDH is RDH12. By immunocytochemistry, ZCRDH was abundantly present in cone inner segments, similar to the reported distribution of RDH12. Finally, RDH12 was the only mammalian candidate protein to exhibit 11cROL-oxidase catalytic activity. These observations suggest that RDH12 in mammals is the functional ortholog of ZCRDH, which allows cones, but not rods, to regenerate visual pigments from 11cROL provided by Müller cells. This capacity permits cones to escape competition from rods for visual chromophore in daylight-exposed retinas.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Células Fotorreceptoras Retinianas Bastones / Células Fotorreceptoras Retinianas Conos / Oxidorreductasas de Alcohol Límite: Animals / Humans Idioma: En Revista: Curr Biol Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Células Fotorreceptoras Retinianas Bastones / Células Fotorreceptoras Retinianas Conos / Oxidorreductasas de Alcohol Límite: Animals / Humans Idioma: En Revista: Curr Biol Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido