Cytosolic retinoic acid binding protein

After entering the cell, retinol and retinoic acid (RA) are bound by separate cytoplasmic proteins. These cytosolic proteins are called cytoplasmic-retinol binding protein (CRBP) artd cytoplasmic retinoic acid-binding protein (CRABP). Two forms of CRBP exist, and tw o forms of CRABP exist. One form of CRiiP occurs mainly In the villi of the small intestines, while the other form occurs in the liver and other organs. One form of CRABP occurs in the skin, while the other form occurs in many tissues. 

An ingenious binding assay for retinoic acid has been developed that depends on the high affinity of all-fran -retinoic acid-binding protein of rat testicular cytosol for its ligand (Shidoji and Hosoya, 1980). Prior treatment of the cytosol with Blue Sepharose reduced nonspecific binding. The detection limit was 3 ng retinoic acid. 

Nuclear-retinoid receptors provide a mechanism of retinoid action, but most likely where expressed, the cytosolic cellular retinoic acid-binding proteins (CRABPs) also affect the ability of retinoids to initiate biological signals (1,2). holo-CBlABP I sequesters retinoic acid (RA) with a value that may be <1 nM, and serves as a high-affinity 2 nM), efficient substrate of RA... 

Ottonello, S, Scita, G, Mantovani, G., Cavazzini, D., and Rossi, G.L (1993) Retinol bound to cellular retinol-binding protein is substrate for cytosolic retinoic acid synthesis /. Biol Chem. 268,27,133-27,142... 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Retinol is oxidized to retinoic acid. Movement from cytosol to nucleus is guided by cellular retinol-binding proteins and cellular retinoic acidbinding proteins. 

Hormones Some lipophilic hormones (e.g. the steroid hormones, thyroxine, retinoic acid and vitamin D) diffuse across the plasma membrane and interact with intracellular receptors in the cytosol or nucleus. Other lipophilic hormones (e.g. the prostaglandins) and hydrophilic hormones (e.g. the peptide hormones insulin and glucagon and the biogenic amines epinephrine and histamine) bind to receptor proteins in the plasma membrane. 

Boerman MH and Napoli JL (1996) Cellular retinol-binding protein-supported retinoic acid synthesis. Relative roles of microsomes and cytosol. Journal of Biological Chemistry 271, 5610-16. 

Boerman, M H. E M. and Napoli, J L. (1996) Cellular retinol-binding protein-supported retinol dehydrogenation in cytosol and microsomes. relative roles in retinoic acid synthesis J Biol. Chem 271, 5610-5616. 

El Akawi, Z. and Napoli, J. L (1994) Rat liver cytosolic retinal dehydrogenase, comparison of 13-cw-, 9-cis-, and all-trans-retinal as substrates and effects of cellular retinoid-binding proteins and retinoic acid on activity. Biochemistry 33, 1938-1943... 

Posch, K. C, Burns, R B, and Napoli, J L. (1992) Biosynthesis of d -trans-retinoic acid from retinal recognition of retinal bound to cellular retinol binding protein (type I) as substrate by a purified cytosolic dehydrogenase J Biol Chem. 267, 19,676-19,682... 

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