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

Jahn, Olaf; Siems, Sophie B; Kusch, Kathrin; Hesse, Dörte; Jung, Ramona B.; Liepold, Thomas; Uecker, Marina; Sun, Ting; Werner, Hauke

doi:10.3389/fncel.2020.00239

Cited by 56 publications

(107 citation statements)

References 104 publications

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“…Pelizaeus-Merzbacher disease (PMD) is an X-linked hypomyelinating leukodystrophy caused by mutation, deletion or duplication of the PLP1 gene. PLP1 , which encodes proteolipid protein (PLP) and its alternative splicing variant DM20, are the most abundant myelin proteins ( Jahn et al, 2020 ). PMD patients typically have a global developmental delay (motor and cognitive) as well as hypotonia, spasticity, and ataxia ( Inoue, 2019 ).…”

Section: Demyelination and Neuronal Damage; Beyond Classical Demyelinmentioning

confidence: 99%

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Duncan

Simkins

Emery

2021

Front. Cell Dev. Biol.

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The myelination of axons by oligodendrocytes is a highly complex cell-to-cell interaction. Oligodendrocytes and axons have a reciprocal signaling relationship in which oligodendrocytes receive cues from axons that direct their myelination, and oligodendrocytes subsequently shape axonal structure and conduction. Oligodendrocytes are necessary for the maturation of excitatory domains on the axon including nodes of Ranvier, help buffer potassium, and support neuronal energy metabolism. Disruption of the oligodendrocyte-axon unit in traumatic injuries, Alzheimer’s disease and demyelinating diseases such as multiple sclerosis results in axonal dysfunction and can culminate in neurodegeneration. In this review, we discuss the mechanisms by which demyelination and loss of oligodendrocytes compromise axons. We highlight the intra-axonal cascades initiated by demyelination that can result in irreversible axonal damage. Both the restoration of oligodendrocyte myelination or neuroprotective therapies targeting these intra-axonal cascades are likely to have therapeutic potential in disorders in which oligodendrocyte support of axons is disrupted.

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Section: Demyelination and Neuronal Damage; Beyond Classical Demyelinmentioning

confidence: 99%

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Duncan

Simkins

Emery

2021

Front. Cell Dev. Biol.

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“…With the aim of routinely exploring the relative abundance of hundreds of proteins in myelin, we chose a peptide intensity-based quantification approach with a data-independent acquisition (DIA) strategy that relies on collecting data in an alternating low and elevated energy mode (referred to as MS E ) and on ion mobility spectrometry to deconvolute spectral complexity (referred to as UDMS E ; reviewed in Distler et al, 2014b). As recently described in detail (Siems et al, 2020), these approaches have allowed us to establish the proteome profiles of myelin in both the CNS and the peripheral nervous system (PNS) of mice (Jahn et al, 2020;Siems et al, 2020). Together, myelin proteome analysis has contributed to the insight that the protein composition of myelin is considerably more complex than initially thought.…”

Section: Introductionmentioning

confidence: 99%

Proteome Profile of Myelin in the Zebrafish Brain

Siems

Jahn

Hoodless

et al. 2021

Front. Cell Dev. Biol.

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The velocity of nerve conduction along vertebrate axons depends on their ensheathment with myelin. Myelin membranes comprise specialized proteins well characterized in mice. Much less is known about the protein composition of myelin in non-mammalian species. Here, we assess the proteome of myelin biochemically purified from the brains of adult zebrafish (Danio rerio), considering its increasing popularity as model organism for myelin biology. Combining gel-based and gel-free proteomic approaches, we identified > 1,000 proteins in purified zebrafish myelin, including all known constituents. By mass spectrometric quantification, the predominant Ig-CAM myelin protein zero (MPZ/P0), myelin basic protein (MBP), and the short-chain dehydrogenase 36K constitute 12%, 8%, and 6% of the total myelin protein, respectively. Comparison with previously established mRNA-abundance profiles shows that expression of many myelin-related transcripts coincides with the maturation of zebrafish oligodendrocytes. Zebrafish myelin comprises several proteins that are not present in mice, including 36K, CLDNK, and ZWI. However, a surprisingly large number of ortholog proteins is present in myelin of both species, indicating partial evolutionary preservation of its constituents. Yet, the relative abundance of CNS myelin proteins can differ markedly as exemplified by the complement inhibitor CD59 that constitutes 5% of the total zebrafish myelin protein but is a low-abundant myelin component in mice. Using novel transgenic reporter constructs and cryo-immuno electron microscopy, we confirm the incorporation of CD59 into myelin sheaths. These data provide the first proteome resource of zebrafish CNS myelin and demonstrate both similarities and heterogeneity of myelin composition between teleost fish and rodents.

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“…Proteome study will require the establishment of a reference database for mass spectroscopy. All these approaches have been used on numerous occasions with myelin prepared from rodents, and in some cases, humans [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ], providing a plethora of data for comparative studies.…”

Section: Discussionmentioning

confidence: 99%

New Species Can Broaden Myelin Research: Suitability of Little Skate, Leucoraja erinacea

Möbius

Hümmert

Ruhwedel

et al. 2021

Life

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Although myelinated nervous systems are shared among 60,000 jawed vertebrates, studies aimed at understanding myelination have focused more and more on mice and zebrafish. To obtain a broader understanding of the myelination process, we examined the little skate, Leucoraja erinacea. The reasons behind initiating studies at this time include: the desire to study a species belonging to an out group of other jawed vertebrates; using a species with embryos accessible throughout development; the availability of genome sequences; and the likelihood that mammalian antibodies recognize homologs in the chosen species. We report that the morphological features of myelination in a skate hatchling, a stage that supports complex behavioral repertoires needed for survival, are highly similar in terms of: appearances of myelinating oligodendrocytes (CNS) and Schwann cells (PNS); the way their levels of myelination conform to axon caliber; and their identity in terms of nodal and paranodal specializations. These features provide a core for further studies to determine: axon–myelinating cell communication; the structures of the proteins and lipids upon which myelinated fibers are formed; the pathways used to transport these molecules to sites of myelin assembly and maintenance; and the gene regulatory networks that control their expressions.

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

Cited by 56 publications

References 104 publications

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Proteome Profile of Myelin in the Zebrafish Brain

New Species Can Broaden Myelin Research: Suitability of Little Skate, Leucoraja erinacea

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