Recognizing the Beauty of Myelination through Identifying Sites of Phospholipid, Protein, and RNA Syntheses and Characterizing Their Movements in Myelin Internodes

We used light, electron microscope and teased fiber autoradiography to show that myelinating Schwann cells synthesize phospholipids and proteins in perinuclear cytoplasm and superficial cytoplasmic channels or Cajal bands (SCC/CB). Neither phospholipid nor protein syntheses occur in paranodal loops, Schmidt-Lanterman incisures or adaxonal cytoplasm. Autoradiographic studies also show that in support of local protein synthesis, RNAs move from the nucleus into perinuclear cytoplasm and out along SCC/CB. Unlike other phospholipids, phosphatidylinositol synthesis occurs extensively in axons. This finding indicates differences in the distributions of phospholipid synthesizing enzymes in smooth endoplasmic reticulum of Schwann cell processes and axoplasm.Autoradiographs of nerves at longer survival times show that tritiated phosphatidylcholine and fucose-labeled glycoproteins move from synthetic sites to outermost myelin lamellae. From there, phosphatidylcholine spreads inward reaching innermost lamellae of thicker sheaths in days. Coupled with retention of fucose glycoproteins in outer myelin lamellae is the presence of fucose glycoprotein synthesized during early myelination in inner lamellae of thicker sheaths, a result consistent with growth of myelin sheaths from inner lamellae out. In this review, we revisit these studies because they provide temporal and spatial perspectives needed in understanding dynamic aspects of myelinogenesis and how myelinating cells respond to injury and from altered gene expression.