EXTRA-TRANSPORT 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 different iation. Retinol-binding protein (RBP) is the specific blood carrier tr ansporting ROL, the precursor of the retinoic acid (RA) hormone, to ta rget tissues. Recently, it was reported that, in addition to the nativ e RBP, two truncated forms of RBP, RBP(1) and RBP(2), are also present in normal serum. RBP(2), the form which has lost the two N-terminal L eu is dramatically increased in serum of patients with chronic renal f ailure (CRF) whereas this form is very low in normal serum. There is s trong evidence that RBP(2) is formed in vitamin A target tissues, and that after its release into blood circulation, it is cleared by the ki dney in healthy people but accumulates in the serum of CRF patients. I t appears that RBP(2) may play an important physiological role in ROL transport and recycling. Within the cell, two cellular retinoic acid-b inding proteins (CRABP-I and -II) and a ROL-binding protein (CRBP-I) r egulate the levels of free RA and ROL. The expression of these retinoi d-binding proteins in a given tissue may reflect the extent of retinoi d metabolism. The most intense traffic of retinoids was found in diffe rentiating keratinocytes, whereas nondifferentiated keratinocytes show ed very low activities, suggesting that retinoids control cell differe ntiation in keratinocytes committed to differentiate. Moreover, these data indicate that normal function of epidermis requires precise amoun ts of CRABP-I and -II and that a dysregulation of these carriers can a lter keratinocyte differentiation by inducing inadequate intracellular levels of RA.