Alternative splicing prevents transferrin secretion during differentiationof a human oligodendrocyte cell line

Transferrin, the iron-transport protein of vertebrate serum, is synthesized mainly in the liver, from which it is secreted into the blood. Transferrin is also synthesized in oligodendrocytes and is an early marker of their di fferentiation. We have analyzed the regulation of transferrin expression in HOG cells, a human oligodendrocyte cell line. Transferrin expression was c orrelated with the appearance of oligodendrocyte differentiation markers wh en cells were exposed to differentiation medium. In contrast to the protein expressed in hepatocytes or in Sertoli cells, transferrin was secreted by neither HOG cells nor immature rat primary oligodendrocytes in vitro. Moreo ver, transferrin appears to be localized in the cytosol and not in the secr etory compartment, as is expected for secreted proteins. This transferrin l ocalization was correlated with the synthesis of a specific transcript, res ulting from an alternative splicing, which leads to the elimination of the signal peptide sequence. These results suggest the existence of a functiona l difference between transferrin synthesized in the brain and in other orga ns such as liver and testis, They are in accordance with the hypothesis tha t transferrin plays a specific role, other than iron transport, in oligoden drocyte maturation and in the myelination process. (C) 2000 Wiley-Liss, Inc .