RETINOID-BINDING PROTEINS IN THE CEREBELLUM AND CHOROID-PLEXUS AND THEIR RELATIONSHIP TO REGIONALIZED RETINOIC ACID SYNTHESIS AND DEGRADATION

The expression of cellular retinoic-acid-binding protein (CRABP) and c ellular retinol-binding protein (CRBP), as well as their relationship to retinoic acid (RA) synthesis and degradation were examined in the d eveloping mouse cerebellum and choroid plexus of the fourth ventricle. The choroid plexus, which expresses the RA-synthesizing retinaldehyde dehydrogenase RALDH-2, is likely to represent a diffusion source of R A for the closely apposed cerebellum, regulating its development. We f ound CRBP to be expressed in the choroid plexus and, in an in-vitro as say, addition of recombinant CRBP to RALDH-2 increased RA synthesis fr om retinaldehyde, with the amount of increase depending on the CRBP/re tinal-dehyde ratio. A technique that characterizes RA-binding proteins according to their isoelectric point showed both CRABP I and CRABP II to be present in the cerebellum and P19 cells, and only CRABP II to b e present in the choroid plexus. With this technique, CRABP I could al so be detected in the HL60 cell line. In addition to the two known aci dic RA-binding proteins CRABP I and II, the cerebellum expressed a thi rd RA-binding protein distinguishable by its neutral isoelectric point ; the same binding protein was also detected in the olfactory bulb, ki dney and testes. We used the RA-binding technique to follow the rate o f elimination of bound RA from the cerebellum. A systemic injection of 0.3 mu mols RA into postnatal day-1 mice was almost completely remove d after 8 hours. These results suggest mechanisms by which the retinoi d-binding protein may regulate the equilibrium of RA synthesis and cat abolism in the cerebellum and choroid plexus.