High impact information on CRABP1

• Here we investigate the CRABP distribution in the developing chick limb bud [1].
• It has been proposed that retinoic acid acts by binding to a cellular retinoic acid-binding protein (CRABP) and then entering the nucleus to alter the pattern of gene activity [1].
• A candidate gene involved in the regulation of endogenous RA concentrations is the gene encoding cellular RA binding protein (CRABP) [2].
• We hypothesize that CRABP plays an important role in normal embryogenesis and that embryonic tissues showing high CRABP expression are susceptible to the adverse effects of excess RA [2].
• CRABP expression was detected in the CNS, the craniofacial mesenchyme, ganglia of the peripheral nervous system, the limb bud, and the visceral arch area [2].

Biological context of CRABP1

• The intracellular retinoic acid binding protein CRABP-I has a high affinity for RA, and is thought to be involved in the mechanism of RA signalling [3].
• First we cloned and sequenced genes and promoter regions of the CRABP-I genes from chicken and the Japanese pufferfish, Fugu rubripes [3].

Anatomical context of CRABP1

• In the chick embryo, CRABP levels are high and CRBP levels are low [4].
• Also sensory axons label intensely with CRABP whereas motor axons do not and in the mixed nerves at the brachial plexus sensory and motor components can be distinguished on this basis [4].
• In brachial segments, both types of interneurons began to express CRABP I at stage (st.) 13+ of the V [5].
• The results indicated that chick-embryo tendon cells contained cellular retinoic acid binding protein (CRABP) [6].
• Subsequently, with the onset of axonal outgrowth, C neurons and PL neurons expressed CRABP I in their cell bodies, axons, and growth cones [5].

Associations of CRABP1 with chemical compounds

• We propose that CRABP could be reducing the effective concentration of retinoic acid reaching the nucleus to a level appropriate for the differential regulation of gene transcription, providing a spatially modulated morphogenetic gradient of information for digit formation [1].
• Since retinoyl beta-glucuronide (RAG) contains a free carboxyl group, we studied the interactions of RAG with cellular retinoic acid-binding protein (CRABP) and nuclear receptors of retinoic acid (RARs), the possible mediators of the biological action of retinoic acid (RA) [7].
• 5. Equilibrium binding studies performed under saturating levels of RA indicated that the retinoid bound to the chick CRABP I with a Kd of 27 nM, a value similar to that reported for the native form of this protein from other species [8].
• The binding of four of these compounds to chick limb bud and axolotl CRABP was tested in sucrose density gradient assays and then their potencies at inducing limb duplications tested [9].
• We also found that the growth-modulating toxins colchicine and quisqualate destroyed selectively different subsets of CRABP-containing amacrine cells [10].

Analytical, diagnostic and therapeutic context of CRABP1

• CRABP-I is well conserved in evolution and shows a specific expression pattern during development, but mice made deficient for the protein by gene targeting appear normal [3].
• We have isolated a partial cDNA clone corresponding to the chicken homolog of CRABP, and performed in situ hybridization experiments on sections of embryos at various stages of development [2].
• By immunocytochemistry, CRABP is localised primarily to the developing nervous system, labelling cells and axons in the mantle layer of the neural tube [4].
• Two retinoic acid-binding proteins, a high molecular weight one (90-100 kDa) (peak A) and CRABP (peak B), were obtained on gel filtration column chromatography of extracts of limb buds of chick embryos [11].
• The distribution of cellular retinoic acid-binding proteins I and II (CRABP I and II) during the first 6 days of chick development has been investigated using immunoblotting [12].

References