TPO1, A MEMBER OF A NOVEL PROTEIN FAMILY, IS DEVELOPMENTALLY-REGULATED IN CULTURED OLIGODENDROCYTES

Although the myelin membrane contains only a small set of major protei ns, more sensitive assays indicate the presence of a plethora of uncha racterized proteins. We have used an antibody perturbation approach to reversibly block the differentiation of prooligodendroblasts into mye linating cells, and, in combination with a differential screening proc edure, identified novel mRNAs that are activated during this period. O ne cDNA, TPO1, recognizes a 5.5-kb mRNA that is strongly up-regulated in oligodendrocytes after release of the differentiation block and tha t is expressed at high levels in brain tissue during active myelinatio n. This cDNA represents at least two mRNAs differing from each other i n their 5'-termini. The TPO1 cDNA contains an open reading frame of 1, 380 bp, encoding a protein of 51.8 kDa with a predicted pi of 9.1 that contains two regions homologous to nonclassic zinc finger motifs. Sub cellular localization studies suggest the enriched presence of TPO1 in spherical structures along the major cytoplasmic processes of oligode ndrocytes. TPO1, along with homologues expressed in testis, placenta, and PC12 cells, form a novel family of proteins with multiple hydropho bic domains possibly serving as membrane spanning regions. We postulat e that in oligodendrocytes, TPO1 encodes a protein factor involved in myelin biogenesis.