Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT).

Abstract

Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.

• Authors: Joanna J Kaylor, Jeremy D Cook, Jacob Makshanoff, Nicholas Bischoff, Jennifer Yong, Gabriel H Travis
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 20 Pg. 7302-7 (May 20 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 24799687 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cone Opsins
• Esters
• Fatty Acids
• Multifunctional Enzymes
• Opsins
• Acetyltransferases
• Retinol O-Fatty-Acyltransferase

Topics

• Acetyltransferases (metabolism)
• Animals
• Catalysis
• Cattle
• Chickens
• Cone Opsins (metabolism)
• Ependymoglial Cells (enzymology)
• Esters (chemistry)
• Fatty Acids (chemistry)
• Gene Expression Profiling
• Gene Expression Regulation, Enzymologic
• HEK293 Cells
• Humans
• Kinetics
• Mice
• Multifunctional Enzymes (metabolism)
• Opsins (metabolism)
• Retina (metabolism)
• Retinol O-Fatty-Acyltransferase (metabolism)