Inhibition of Protein Synthesis During CNS Myelination Produces Focal Accumulations of Membrane Vesicles in Oligodendrocytes

This paper described studies to better characterize the membrane vesicles noted in the cold block of myelinating nerves.  It was hypothesized that the membrane vesicles were membrane normally destined to be inserted into the expanding myelin sheath but unable to do so because of altered protein synthesis that prevented the production of a key component(s) necessary for proper myelin formation.

Using ³⁵S-methionine incorporation experiments, polyacrylamide gel electrophoresis and electron microscopy, it was shown that vesicle accumulations similar to those seen by cold block could be produced by direct and local inhibition of protein synthesis.  A drug that inhibited cholesterol lipid synthesis did not produce the same membrane accumulations, and biochemical work from other laboratories confirmed that myelin-specific lipids continue to be synthesized in protein synthesis-inhibited glial cells.  It appeared from our studies that specific and coordinated lipid and protein associations are necessary for the proper assembly and stabilization of the membranes in the paranodal regions of the developing myelin sheath.  The cellular routes and mechanisms of coordination of myelin protein and lipid pools are still largely unknown.