Lipid second messengers and related enzymes in vertebrate rod outer segments

Abstract

outer segment of the cell is comprised of a stack of many hundreds of densely packed discs, each of which represents a double layer of infolded plasma membrane. It has been suggested that phospholipid moieties in these membranes are metabolically active and are closely involved in the generation of physiological mediators. Modifi cations in the metabolism of photoreceptor membrane glycerolipids have been linked to the transduction of visual stimuli ( 3 ). Rod outer segment (ROS) membranes are composed of 50% protein and 50% lipid, by weight ( 2 ). Phospholipids and cholesterol represent nearly 90-95% and 4-6% (w/w) of total lipids, respectively. Rhodopsin accounts for at least 80-85% (w/w) of the total proteins ( 4-6 ) in disc ROS membranes. The rest are mainly proteins involved in phototransduction. The composition of mammalian ROS membrane phospholipids indicates that the major phospholipids are phosphatidylethanolamine (PE) and phosphatidylcholine (PC), along with relatively large amounts of phosphatidylserine (PS) (15%). Small amounts (less than 1% each) of sphingomyelin, phosphatidylinositol (PI) and phosphatidic acid (PA) are found in these membranes ( 7-13 ). In vertebrates, cholesterol (exclusively as the free sterol) is the principal neutral lipid, comprising The vertebrate photoreceptor cell is composed of different cellular compartments [outer segment (OS), inner segment (IS), and synaptic terminal (ST)], all of which differ in their lipid and protein content ( 1, 2 ). The photoreceptor is a highly specialized cell that responds to light stimulus and transmits this response to adjoining neurons for ultimate relay to the visual centers of the brain. TheThis work was supported

Neuropathy target esterase impairments cause Oliver–McFarlane and Laurence–Moon syndromes

“…Trichomegaly results from increased prostaglandin production due to increased phosphatidylethanolamine in follicular cells 46. Retinal degeneration may relate to abnormalities of multiple membrane phospholipid functions, including outer segment disc membrane formation in photoreceptor cells, lipid second messengers in visual transduction, degeneration of optic nerve axons and vitamin A analogue processing or melanosome trafficking in RPE 47 48. Notably, carriers of alleles associated with Oliver–McFarlane/Laurence–Moon appear completely unaffected, though their cells exhibit similar or reduced function compared with SPG39 patients, suggesting that biallelic mutations are required to confer disease status.…”

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

“…Lipids diverse roles as signaling molecules have been previously reviewed (Bazan, 2003; Giusto et al, 2010; Marrache et al, 2005; Shimizu, 2009) and will not be explored here. It is not yet known which lipids can be used as fuel so we will also discuss the general lipid composition of the retina as well retinal lipid metabolism, including fatty acids biosynthesis in the endoplasmic reticulum and lipid degradation and oxidation in peroxisomes and mitochondria.…”

Light-Induced Tyrosine Phosphorylation of Rod Outer Segment Membrane Proteins Regulate the Translocation, Membrane Binding and Activation of Type II α Phosphatidylinositol-5-Phosphate 4-Kinase

“…Modulation of phototransduction gain by changes in phosphoinositide levels has been reported [22]. Further, the light-dependent translocation of phototransduction proteins influences the enzymatic activities of phospholipase D, lipid phosphate phosphatase, diacylglyceride lipase and diacylglyceride kinase, all of which are responsible for the generation of the second messenger molecules [23–25]. …”