Lipids and Myelination

Abstract

In the spirit of a workshop, I will discuss possibilities of there being two independent mechanisms for the entry of lipids into the myelin sheath. These proposed mechanisms would work separately, though not necessarily independently, to deploy different lipids in the cytoplasmic and external sides, respectively, of the ‘asymmetric’ bilayer membrane. Before elaborating on these mechanisms, I will discuss pertinent material under six topics: (1) need for myelin, (2) myelin lipid composition, (3) dynamics of myelin lipids, (4) metabolism of sphingomyelin, ethanolamine plasmalogen, phosphatidylserine and phosphatidylinositol 4,5-bisphosphate, (5) cholesterol metabolism and (6) glycolipid metabolism. The strategies used to provide myelin with the abovementioned phospholipids, with cholesterol and with glycolipids will then be integrated with our current picture of myelin protein assembly (e.g. Colman et al., this volume). The relatedness of the dual mechanisms for proteins and lipids will be stressed. One mechanism involves the Golgi apparatus as the sorting station for integral proteins (as proteolipid protein and P0) and certain glycolipids to the external leaflet. The other mechanism is based at (or near) the plasma membrane or in adjacent myelin, to rapidly sequester myelin basic proteins and certain phospholipids into the cytoplasmic face of compact myelin.