CRABP

Adapalene (Table 1), a new highly stable naphtoic acid arotinoid with lipophilic properties, does not bind to CRABP, although it enhances its synthesis, and its rank-order of retinoid receptor affinity apears to be RAR(3 > RARy > > RARa. 

Nematodes provide exceptions to the rule that members of the FABP/ P2/CRBP/CRABP family of proteins are universally intracellular. Some of those secreted by nematodes may be involved in specialized functions, such as the protection of developing embryos within shelled eggs. Nematodes also provide examples of where the highly conserved tertiary structure of these proteins has been modified. 

CRABP-GST is immobilized onto a glutathione-containing resin at a concentration that saturates the resin. A complex lipid mixture was prepared by combining a concentrated lipid extract derived from mouse tissue (brain) [5] (DMSO stock) with exogenously added retinoic acid (RA, positive control) and 13C-oleic acid (negative control). Analysis of this complex lipid mixture by LC-MS prior to incubation with immobilized CRABP demonstrated that the mixture contained RA (added), phospholipids, acylglycerols, cholesterol esters, and cholesterol. A portion of this mixture (corresponding to 1 nmol of RA) was added to PBS (DMSO concentration should not exceed 5%) and incubated with the CRABP-GST bound beads for 1 h. 

After analysis of the CRABP-GST samples with XCMS, two statistically significant ions (m/z 299 and 279) were identified. Based on co-elution with known standards and accurate mass, these ions were confirmed to correspond to RA and linoleic acid (08 2 free fatty acid) (Fig. 11). The fold change for RA ( 14-fold) is much larger than for linoleic acid (twofold), as would be expected for CRABP. 

Fig. 11 Data from metabolomics PMI experiments, (a) Enrichment of retinoic acid by CRABP-GST from a mixture of brain lipids ( P < 0.01, n = 3 1, Student s t-test). (b) StarD3-mediated enrichment of cholesterol from a brain lipid extract...

Anhydroretinol binds to plasma and intracellular RBPs, but not to the cellular retinoic acid binding proteins (CRABPs) or retinoid receptors. In experimental animals, it protects against the development of chemically induced tumors while showing none of the toxic effects of other retinoids. 

Cellular Retinoid Binding Proteins CRBPs and CRABPs... 

CRABP(II) occurs primarily in the skin, utems, ovary, choroid plexus, and in fetal cells. 

M five proteins have a high affinity and are present in excess of their ligands, with CRBP 1.4-fold higher than intracellular retinol, and CRABP 20-fold higher than intracellular retinoic acid. This means that, under normal conditions, essentially all of the intracellular retinoids will be protein-bound. 

CRABP (1) and CRABP (11) function to transport retinoic acid into the nucleus for binding to retinoid receptors. CRABP(ll), with retinoic acid bound, also interacts directly with the liganded RAR-RXR heterodimer bound to hormone response elements on DNA and enhances the activity of the nuclear receptor (Section2.3.2.1 Delvaetal., 1999). 

Both CRBP and CRABP are also important in regulating the metabolism of retinoids ... 

CRABP is required for the microsomal oxidation of retinoic acid to more... 

Retinoic acid may either enter the target cell from the circulation or may be formed intraceUularly by oxidation of retinol. A number of tissues - but not muscle, kidneys, small intestines, liver, lungs, or spleen - have a cellular retinoic acid binding protein (CRABP) that is distinct from CRBP. Testis and... 

The two families of receptors differ from each other considerably, and RARs show greater sequence homology with thyroid hormone receptors than with RXRs. RARs act only as heterodimers with RXRs homodimers of RARs have poor affinity for retinoid response elements on DNA. The liganded CRABP(II) enhances the binding of the RAR-RXR heterodimer to response elements on DNA and amplifies the effect of the receptor dimer (Delva et al., 1999). 

Momoi T, Hanaoka K, and Momoi M (1990) Spatial and temporal expression of cellular retinoic acid binding protein (CRABP) along the anteroposterior axis in the central nervous system of mouse embryos. Biochemical and Biophysical Research Communications 169, 991-6. 

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