On the biogenesis of myelin membranes: Sorting, trafficking and cell polarity

Abstract

In the central nervous system, a multilayered membrane layer known as the myelin sheath enwraps axons, and is required for optimal saltatory signal conductance. The sheath develops from membrane processes that extend from the plasma membrane of oligodendrocytes and displays a unique lipid and protein composition. Myelin biogenesis is carefully regulated, and multiple transport pathways involving a variety of endosomal compartments are involved. Here we briefly summarize how the major myelin proteins proteolipid protein and myelin basic protein reach the sheath, and highlight potential mechanisms involved, including the role of myelin specific lipids and cell polarity related transport pathways.

Transport of the Major Myelin Proteolipid Protein Is Directed by VAMP3 and VAMP7

“…The cellular mechanisms of myelin formation are not well understood, but indeed essential to fully grasp pathology of myelin disease and to tackle the problem of inefficient remyelination associated with most diseases including multiple sclerosis. A major challenge for oligodendrocytes, which ensheath multiple axon segments simultaneously, is the temporal and spatial orchestration of myelin membrane synthesis and traffic to control membrane domain morphogenesis and the directed growth of the emerging myelin sheath (Krämer et al, 2001;Baron and Hoekstra, 2010). Several myelin proteins undergo distinct endocytic sorting and recycling associated with plasma membrane remodeling (Winterstein et al, 2008).…”

Transcriptional Expression of Myelin Basic Protein in Oligodendrocytes Depends on Functional Syntaxin 4: a Potential Correlation with Autocrine Signaling

“…Therefore, in this work, we examined whether syntaxins 3 and 4 are functionally expressed in rat primary OLGs and involved in myelin biogenesis, thereby focusing on the role of myelin sheet-localized syntaxins and the two major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). These proteins are expressed in a timely fashion and sorted and transported to the myelin membrane by different mechanisms (1,20,21). MBP, located at the cytoplasmic surface of myelin membranes, is a basic, membrane-associated adhesive protein and essential for myelination in vivo (22)(23)(24).…”

“…Furthermore, MBP appears to act as a portal for protein entry into myelin membranes (7). MBP is transported to the myelin sheath in its mRNA form (26,27), which is thought to circumvent premature adhesion of membranes (1,22,24,25). Although MBP mRNA is assembled in nonmembranous granules (26)(27)(28), a causal relationship with the vesicular transport ma-chinery is likely, given that membrane trafficking appears to be involved in RNA transport and/or anchoring (29)(30)(31).…”

“…Importantly, the apical and basolateral plasma membrane domains of polarized epithelial cells contain distinct t-SNAREs (11), i.e., syntaxins 3 and 4, which are preferentially localized at the apical and basolateral plasma membrane, respectively (12)(13)(14)(15)(16)(17). Both syntaxin 3 and syntaxin 4 are known to be present in OLGs (1,18,19), but their functional role in myelin biogenesis is still largely unknown. Therefore, in this work, we examined whether syntaxins 3 and 4 are functionally expressed in rat primary OLGs and involved in myelin biogenesis, thereby focusing on the role of myelin sheet-localized syntaxins and the two major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP).…”

“…Like the apical and basolateral plasma membrane domains in polarized epithelial cells, the myelin-like membrane (sheet) and cell body plasma membrane can be considered a reflection of the polarized nature of cultured OLGs (1). Indeed, in previous work, we observed that distinct viral proteins, i.e., the hemagglutinin (HA) of influenza virus and the glycoprotein of vesicular stomatitis virus (VSV G), which are sorted and transported in epithelial cells to the apical and basolateral domains, respectively, also display a distinct and preferential localization in cultured OLGs (2).…”