Members of the myelin-associated oligodendrocytic basic protein (MOBP) family constitute the third most abundant protein in CNS myelin. Although MOBP localizes to the major dense line (MDL) of CNS myelin, the function of the individual isoforms is unknown. Alternative splicing of pre-Mobp mRNA gives rise to six characterized splice variants in both the mouse and the rat. These splice variants share a common N-terminal encoded in Mobp exon 3 comprising 68 amino acids. The predicted protein isoforms differ in their C-termini. Sequence analysis of intron 3 revealed the presence of a putative initiation codon followed by an open reading frame (ORF) encoding 53 amino acids that extends in frame into Mobp exon 4 yielding a predicted MOBP isoform comprising 155 amino acids, designated MOBP155. This newly characterized isoform possessing a novel N-terminus shares a common C-terminus with MOBP170. Mobp170 message is detectable at low abundance throughout myelinogenesis. In contrast, the novel splice variant encoding MOBP155 is expressed at modest levels late in CNS development, coincident with the expression of the abundant splice variant, Mobp81A. Immunostaining of Cos7 cells transiently expressing an epitope-tagged MOBP155 suggested that most of the product was translocated to mitochondria. Although Mobp155 and Mobp170 encode a common predicted C-terminus they have different expression profiles and their products are targeted to mitochondria and the nucleus, respectively, in transiently transfected Cos7 cells.
2004 Wiley-Liss, Inc.