The Role of Vesicle Trafficking and Release in Oligodendrocyte Biology

Abstract

Oligodendrocytes are a subtype of glial cells found within the central nervous system (CNS), responsible for the formation and maintenance of specialized myelin membranes which wrap neuronal axons. The development of myelin requires tight coordination for the cell to deliver lipid and protein building blocks to specific myelin segments at the right time. Both internal and external cues control myelination, thus the reception of these signals also requires precise regulation. In late years, a growing body of evidence indicates that oligodendrocytes, like many other cell types, may use extracellular vesicles (EVs) as a medium for transferring information. The field of EV research has expanded rapidly over the past decade, with new contributions that suggest EVs might have direct involvement in communications with neurons and other glial cells to fine tune oligodendroglial function. This functional role of EVs might also be maladaptive, as it has likewise been implicated in the spreading of toxic molecules within the brain during disease. In this review we will discuss the field's current understanding of extracellular vesicle biology within oligodendrocytes, and their contribution to physiologic and pathologic conditions.

Keywords: Axon-glial communication; Demyelination; Exosomes; Extracellular vesicles; Microvesicles; Myelin; Oligodendrocytes; Remyelination; Sphingolipids.

Figure 1.. Extracellular Vesicle Release and Uptake

Within the donor cell, cargo is sorted from various organelles and targeted for extracellular vesicle (EV) incorporation by cargo- and context-dependent mechanisms. EVs are formed by 2 major pathways: inward budding into an endosome to form a multivesicular body (MVB), or by direct outward budding of the plasma membrane (PM). Both methods employ multiple molecular components to alter membrane topology, such as ESCRT proteins and the lipid ceramide. Vesicles released from the MVB following SNARE protein facilitated fusion with the PM are termed exosomes, while the vesicles derived from PM fission are microvesicles. Heterogenous populations of EVs traverse interstitium and systemic circulation to reach their target, where they may bind to surface receptors, fuse with the cell membrane, or be internalized by the recipient cell to execute their function