Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon, Yannick; Kopec, Ashley M.; Belin, Sophie

doi:10.3390/cells9040812

Cited by 183 publications

(129 citation statements)

References 170 publications

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“…Unlike MBP and P0ct, however, P2 binds membrane surfaces in a reversible manner [ 21 , 130 ], which could enable P2 to have a more transient role in compact myelin. This has implications e.g., during the maintenance of myelin via lipid replenishment, which is a pre-requisite for the long-term integrity of myelin [ 131 , 132 , 133 , 134 , 135 ]. P2 is an important component of PNS myelin, as several mutations lead to CMT [ 136 , 137 , 138 , 139 , 140 ] by affecting the structure-function relationships of P2 [ 141 ].…”

Section: P0 Is the Executive Pns Membrane Stackermentioning

confidence: 99%

How Does Protein Zero Assemble Compact Myelin?

Raasakka

Kursula

2020

Cells

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Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin—the lipid-rich, periodic structure of membrane pairs that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes via homophilic adhesion, forming, as revealed by electron microscopy, the electron-dense, double “intraperiod line” that is split by a narrow, electron-lucent space corresponding to the extracellular space between membrane pairs. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs myelination. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when P0 is trafficked and modified to enable myelin compaction, and how mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies.

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Section: P0 Is the Executive Pns Membrane Stackermentioning

confidence: 99%

How Does Protein Zero Assemble Compact Myelin?

Raasakka

Kursula

2020

Cells

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“…In the central nervous system (CNS) of vertebrates, the velocity of nerve conduction is accelerated by the insulation of axons with multiple layers of myelin membrane provided by oligodendrocytes ( Nave and Werner, 2014 ; Snaidero and Simons, 2017 ). Compared to other cellular membranes myelin is unusually enriched for lipids, in particular cholesterol, galactolipids and plasmalogens ( Norton and Poduslo, 1973a ; Schmitt et al, 2015 ; Poitelon et al, 2020 ). Indeed, the biogenesis of myelin may involve the coalescence of lipid-rich membrane-microdomains in the oligodendroglial secretory pathway ( Lee, 2001 ; Chrast et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

The CNS Myelin Proteome: Deep Profile and Persistence After Post-mortem Delay

Jahn

Siems

Kusch

et al. 2020

Front. Cell. Neurosci.

100

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Myelin membranes are dominated by lipids while the complexity of their protein composition has long been considered to be low. However, numerous additional myelin proteins have been identified since. Here we revisit the proteome of myelin biochemically purified from the brains of healthy c56Bl/6N-mice utilizing complementary proteomic approaches for deep qualitative and quantitative coverage. By gel-free, label-free mass spectrometry, the most abundant myelin proteins PLP, MBP, CNP, and MOG constitute 38, 30, 5, and 1% of the total myelin protein, respectively. The relative abundance of myelin proteins displays a dynamic range of over four orders of magnitude, implying that PLP and MBP have overshadowed less abundant myelin constituents in initial gel-based approaches. By comparisons with published datasets we evaluate to which degree the CNS myelin proteome correlates with the mRNA and protein abundance profiles of myelin and oligodendrocytes. Notably, the myelin proteome displays only minor changes if assessed after a post-mortem delay of 6 h. These data provide the most comprehensive proteome resource of CNS myelin so far and a basis for addressing proteomic heterogeneity of myelin in mouse models and human patients with white matter disorders.

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“…1c). The downregulation of these pathways is of great interest given that the major lipid classes of myelin are 1) cholesterol, 2) phospholipid, including plasmalogen, phosphatidylcholine (PC), and sphingomyelin (SM), and 3) glycolipid, including glycosphingolipids such as glucosylceramide (CerG) and sulfatide 35 (Fig. 1d).…”

Section: Resultsmentioning

confidence: 99%

Influenza causes alterations to oligodendrocyte-specific transcripts and the myelin lipidome in the adult mouse central nervous system.

Louie

Kim

Soto-Diaz

et al. 2021

Preprint

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The notion that myelin remains static during adulthood has been challenged in recent years. Myelin is not only crucial for proper cognitive function and behavior, but it is vulnerable to alterations from external factors outside the window of development. Here, in the adult mouse CNS, RNA analysis revealed global downregulation and subsequent recovery of oligodendrocyte-specific transcripts in response to peripheral influenza viral infection. Furthermore, shot-gun lipidomic analysis revealed that infection alters the lipid profile in the prefrontal cortex as well as in purified brain myelin. Finally, treatment with the colony stimulating factor receptor (CSFR)1 antagonist GW2580 during infection suppressed glial activation and partially restored oligodendrocyte-specific myelin transcripts to baseline levels. Together, these findings reveal a yet unforeseen consequence of peripheral infection on oligodendrocyte homeostasis in the adult mouse.

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Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Cited by 183 publications

References 170 publications

How Does Protein Zero Assemble Compact Myelin?

How Does Protein Zero Assemble Compact Myelin?

The CNS Myelin Proteome: Deep Profile and Persistence After Post-mortem Delay

Influenza causes alterations to oligodendrocyte-specific transcripts and the myelin lipidome in the adult mouse central nervous system.

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