CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process

Szuchet, Sara; Nielsen, Lauren L.; Domowicz, Miriam S.; Austin, Jotham R.; Arvanitis, Dimitrios L.

doi:10.1016/j.jsb.2015.01.015

Cited by 17 publications

(14 citation statements)

References 73 publications

(80 reference statements)

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“…That is, a specific set of lipids and proteins have to be correctly assembled on the myelin membrane in time. 40 In most cells, the majority molecules localizing to the internal vesicles of the endosomal system are destined for lysosomal degradation by lysosomal proteases. However, in OLs, LE/L compartments may be particularly useful as storage compartments, as they are able to harbor a large amount of membrane materials for myelin biogenesis in a multilamellar and multivesicularmanner.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

et al. 2018

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This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells. In addition, the relevant molecular mechanism was explored by immunoprecipitation. The increase in Fluoromyelin Green staining and proteolipid protein expression was not significant in the corpus callosum of CathD−/− mice at the age of P11, P14 and P24. Proteolipid protein expression was weak at each time point and was mostly accumulated around the nucleus. The number of oligodendrocyte lineage cells (olig2+) and mature oligodendrocytes (CC1+) significantly decreased between P14 and P24. In the oligodendrocyte precursor cell culture of CathD−/− mice, the morphology of myelin basic protein-positive mature oligodendrocytes was simple while oligodendrocyte precursor cells showed delayed differentiation into mature oligodendrocytes. Moreover, more proteolipid protein gathered in late endosomes/lysosomes (LEs/Ls) and fewer reached the plasma membrane. Immunohistochemistry and immunoelectron microscopy analysis showed that CathD, proteolipid protein and VAMP7 could bind with each other, whereas VAMP7 and proteolipid protein colocalized with CathD in late endosome/lysosome. The findings of this paper suggest that CathD may have an important role in the myelination of CNS, presumably by altering the trafficking of proteolipid protein.

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Section: Discussionmentioning

confidence: 99%

Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

et al. 2018

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“…Myelin is formed by the plasma membrane of oligodendrocytes (in the CNS) or Schwann cells (in the peripheral nervous system) wrapping around axon segments many times (Szuchet et al, 2015 ) and forming a compacted insulating sheath, that serves to improve the speed and efficiency of electrical signal conduction along the myelinated axon. Myelination is a dynamic process that can be modulated by the axonal release of neurotransmitter and by environmental factors.…”

Section: Glial Contributions To Brain Developmentmentioning

confidence: 99%

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective

Wilhelm

Guizzetti

2016

Front. Integr. Neurosci.

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Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.

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“…In the case of OLs, they extend their processes spirally inward, around the axons, in a corkscrew-like manner to lay down a multi-lamellar, compact, lipid rich sheath (myelin sheath; myelin from myelós, Greek for marrow) on the axons. Formation of the myelin sheath occurs in an outside to inside fashion by a process involving homotypic fusion of myelinophore organelles within the confines of their processes (Ioannidou et al, 2012 ; Snaidero et al, 2014 ; Szuchet et al, 2015 ). OLs represent almost 75% of the neocortical glial population, and each OL is capable of laying down myelin on 40–60 short axonal segments of multiple CNS axons with varying diameter (Matthews and Duncan, 1971 ; Lubetzki et al, 1993 ; Shaham, 2006 ; Pelvig et al, 2008 ; Fields et al, 2015 ).…”

Section: Myelinating Glia Of the Cns And Pnsmentioning

confidence: 99%

“…Myelination is a multistage process with considerable overlap among its different phases. In general, these phases involve: (1) the migration and ensuing differentiation of glial precursors into mature myelinating glia; (2) the initial recognition of the axon, axon-glia contact, axonal segment selection and subsequent ensheathment of the target axonal segments by the myelinating glia; (3) the initiation of myelin-associated protein expression in the myelinating glia and finally; (4) the compaction and maturation of the myelin sheath (Szuchet et al, 2015 ). Further fine-tuning of the myelination process involves the generation of functional axonal domains such as nodes of Ranvier, paranodes and juxtaparanodes.…”

Section: Myelinating Glia Of the Cns And Pnsmentioning

confidence: 99%

Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration

Rao

Pearse

2016

Front. Mol. Neurosci.

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Following spinal cord injury (SCI), a multitude of intrinsic and extrinsic factors adversely affect the gene programs that govern the expression of regeneration-associated genes (RAGs) and the production of a diversity of extracellular matrix molecules (ECM). Insufficient RAG expression in the injured neuron and the presence of inhibitory ECM at the lesion, leads to structural alterations in the axon that perturb the growth machinery, or form an extraneous barrier to axonal regeneration, respectively. Here, the role of myelin, both intact and debris, in antagonizing axon regeneration has been the focus of numerous investigations. These studies have employed antagonizing antibodies and knockout animals to examine how the growth cone of the re-growing axon responds to the presence of myelin and myelin-associated inhibitors (MAIs) within the lesion environment and caudal spinal cord. However, less attention has been placed on how the myelination of the axon after SCI, whether by endogenous glia or exogenously implanted glia, may alter axon regeneration. Here, we examine the intersection between intracellular signaling pathways in neurons and glia that are involved in axon myelination and axon growth, to provide greater insight into how interrogating this complex network of molecular interactions may lead to new therapeutics targeting SCI.

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CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process

Cited by 17 publications

References 73 publications

Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective

Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration

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