Extra-and intracellular transport of retinoids: a reappraisal.

Retinoids are a family of compounds including retinol (ROL; vitamin A) and ROL derivatives that exert a powerful control over cell differentiation. Retinol-binding protein (RBP) is the specific blood carrier transporting ROL, the precursor of the retinoic acid (RA) hormone, to target tissues. Recently, it was reported that, in addition to the native RBP, two truncated forms of RBP, RBP1 and RBP2, are also present in normal serum. RBP2, the form which has lost the two N-terminal Leu is dramatically increased in serum of patients with chronic renal failure (CRF) whereas this form is very low in normal serum. There is strong evidence that RBP2 is formed in vitamin A target tissues, and that after its release into blood circulation, it is cleared by the kidney in healthy people but accumulates in the serum of CRF patients. It appears that RBP2 may play an important physiological role in ROL transport and recycling. Within the cell, two cellular retinoic acid-binding proteins (CRABP-I and -II) and a ROL-binding protein (CRBP-I) regulate the levels of free RA and ROL. The expression of these retinoid-binding proteins in a given tissue may reflect the extent of retinoid metabolism. The most intense traffic of retinoids was found in differentiating keratinocytes, whereas nondifferentiated keratinocytes showed very low activities, suggesting that retinoids control cell differentiation in keratinocytes committed to differentiate. Moreover, these data indicate that normal function of epidermis requires precise amounts of CRABP-I and -II that a dysregulation of these carriers can alter keratinocyte differentiation by inducing inadequate intracellular levels of RA.