Alternative splicing prevents transferrin secretion during differentiation of 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 differentiation. We have analyzed the regulation of transferrin expression in HOG cells, a human oligodendrocyte cell line. Transferrin expression was correlated with the appearance of oligodendrocyte differentiation markers when 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. Moreover, transferrin appears to be localized in the cytosol and not in the secretory compartment, as is expected for secreted proteins. This transferrin localization was correlated with the synthesis of a specific transcript, resulting from an alternative splicing, which leads to the elimination of the signal peptide sequence. These results suggest the existence of a functional difference between transferrin synthesized in the brain and in other organs such as liver and testis. They are in accordance with the hypothesis that transferrin plays a specific role, other than iron transport, in oligodendrocyte maturation and in the myelination process.
de Arriba Zerpa
G A
GA
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Saleh
M C
MC
Fernández
P M
PM
Guillou
F
F
Espinosa de los Monteros
A
A
de Vellis
J
J
Zakin
M M
MM
Baron
B
B
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003470:Culture Media / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014168:Transferrin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D014168:Transferrin