Myelin basic protein mRNA localization and polypeptide targeting

Abstract

Myelin basic proteins (MBPs), the major peripheral membrane proteins of central nervous system (CNS) myelin, are encoded by mRNAs that are selectively segregated to the myelinating processes of oligodendrocytes. In order to test whether the intracellular mechanisms responsible for MBP mRNA translocation are oligodendrocyte-specific, or alternatively, are present in other cell types and may therefore be more general, we have studied the localization of the 14 kD MBP mRNA and its encoded polypeptide (MBP14) in transiently transfected HeLa cells (a cervical carcinoma cell line) and in the rat pheochromocytoma cell line PC12. Unlike the situation in oligodendrocytes in situ, where MBP mRNAs are translocated and become "centrifugally" distributed, in both of the non-glial cells MBP mRNA was primarily detected in the perinuclear region. The MBP14 polypeptide was found associated with intracellular membranes, and not exclusively with the plasma membrane. Our results indicate that the inability of HeLa and PC12 cells to correctly target MBP mRNAs to the cell periphery leads to a failure to incorporate MBP polypeptides directly into the plasma membrane. Further, the data lend credence to the concept that MBP mRNA segregation appears to be a specific feature of myelin-forming cells which is required for the precise delivery of the encoded polypeptides to the forming myelin membrane.