Möbius, Wiebke

[["dc.bibliographiccitation.artnumber","e1006290"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","PLoS genetics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Hu, Bo"],["dc.contributor.author","Arpag, Sezgi"],["dc.contributor.author","Zhang, Xuebao"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke"],["dc.contributor.author","Sosinsky, Gina"],["dc.contributor.author","Ellisman, Mark"],["dc.contributor.author","Zhang, Yang"],["dc.contributor.author","Hamilton, Audra"],["dc.contributor.author","Chernoff, Jonathan"],["dc.contributor.author","Li, Jun"],["dc.date.accessioned","2019-07-09T11:42:46Z"],["dc.date.available","2019-07-09T11:42:46Z"],["dc.date.issued","2016-09-01"],["dc.description.abstract","Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it \"functional demyelination\", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP."],["dc.identifier.doi","10.1371/journal.pgen.1006290"],["dc.identifier.pmid","27583434"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58738"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1553-7404"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e3000943"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Gregor, Ingo"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Köhler, Susanne"],["dc.contributor.author","Restrepo, Alejandro"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2021-04-14T08:31:16Z"],["dc.date.available","2021-04-14T08:31:16Z"],["dc.date.issued","2020"],["dc.description.abstract","In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plpnull/y mouse model of spastic paraplegia. Optic nerves from Plpnull/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plpnull/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon–myelin unit contribute to the phenotype of Plpnull/y mice."],["dc.identifier.doi","10.1371/journal.pbio.3000943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83539"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/20"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | P08: Strukturelle und funktionale Veränderungen der inneren mitochondrialen Membran axonaler Mitochondrien in vivo in einem dymyelinisierenden Mausmodell"],["dc.relation.eissn","1545-7885"],["dc.relation.workinggroup","RG Möbius"],["dc.rights","CC BY 4.0"],["dc.title","Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","111"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuron Glia Biology"],["dc.bibliographiccitation.lastpage","127"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2022-03-01T11:45:38Z"],["dc.date.available","2022-03-01T11:45:38Z"],["dc.date.issued","2009"],["dc.description.abstract","The protein composition of myelin in the central nervous system (CNS) has changed at the evolutionary transition from fish to tetrapods, when a lipid-associated transmembrane-tetraspan (proteolipid protein, PLP) replaced an adhesion protein of the immunoglobulin superfamily (P0) as the most abundant constituent. Here, we review major steps of proteolipid evolution. Three paralog proteolipids (PLP/DM20/DMα, M6B/DMγ and the neuronal glycoprotein M6A/DMβ) exist in vertebrates from cartilaginous fish to mammals, and one (M6/CG7540) can be traced in invertebrate bilaterians including the planktonic copepod Calanus finmarchicus that possess a functional myelin equivalent. In fish, DMα and DMγ are coexpressed in oligodendrocytes but are not major myelin components. PLP emerged at the root of tetrapods by the acquisition of an enlarged cytoplasmic loop in the evolutionary older DMα/DM20. Transgenic experiments in mice suggest that this loop enhances the incorporation of PLP into myelin. The evolutionary recruitment of PLP as the major myelin protein provided oligodendrocytes with the competence to support long-term axonal integrity. We suggest that the molecular shift from P0 to PLP also correlates with the concentration of adhesive forces at the radial component, and that the new balance between membrane adhesion and dynamics was favorable for CNS myelination."],["dc.description.abstract","The protein composition of myelin in the central nervous system (CNS) has changed at the evolutionary transition from fish to tetrapods, when a lipid-associated transmembrane-tetraspan (proteolipid protein, PLP) replaced an adhesion protein of the immunoglobulin superfamily (P0) as the most abundant constituent. Here, we review major steps of proteolipid evolution. Three paralog proteolipids (PLP/DM20/DMα, M6B/DMγ and the neuronal glycoprotein M6A/DMβ) exist in vertebrates from cartilaginous fish to mammals, and one (M6/CG7540) can be traced in invertebrate bilaterians including the planktonic copepod Calanus finmarchicus that possess a functional myelin equivalent. In fish, DMα and DMγ are coexpressed in oligodendrocytes but are not major myelin components. PLP emerged at the root of tetrapods by the acquisition of an enlarged cytoplasmic loop in the evolutionary older DMα/DM20. Transgenic experiments in mice suggest that this loop enhances the incorporation of PLP into myelin. The evolutionary recruitment of PLP as the major myelin protein provided oligodendrocytes with the competence to support long-term axonal integrity. We suggest that the molecular shift from P0 to PLP also correlates with the concentration of adhesive forces at the radial component, and that the new balance between membrane adhesion and dynamics was favorable for CNS myelination."],["dc.identifier.doi","10.1017/S1740925X0900009X"],["dc.identifier.pii","S1740925X0900009X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103398"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1741-0533"],["dc.relation.issn","1740-925X"],["dc.title","Phylogeny of proteolipid proteins: divergence, constraints, and the evolution of novel functions in myelination and neuroprotection"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","567"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","586"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Kraemer-Albers, Eva-Maria"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Tenzer, Stefan"],["dc.contributor.author","Ohno-Iwashita, Yoshiko"],["dc.contributor.author","Monasterio-Schrader, Patricia de"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Griffiths, Ian R."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2017-09-07T11:47:44Z"],["dc.date.available","2017-09-07T11:47:44Z"],["dc.date.issued","2013"],["dc.description.abstract","The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that high cholesterol is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. (c) 2013 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/glia.22456"],["dc.identifier.gro","3142368"],["dc.identifier.isi","000314981400010"],["dc.identifier.pmid","23322581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7508"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: BMBF; European Commission"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.title","A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","65"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Uecker, Martin"],["dc.contributor.author","Liepold, Thomas"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Valerius, Oliver"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2018-11-07T10:23:03Z"],["dc.date.available","2018-11-07T10:23:03Z"],["dc.date.issued","2017"],["dc.identifier.isi","000403071700600"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42387"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.publisher.place","Hoboken"],["dc.relation.conference","13th European Meeting on Glial Cells in Health and Disease"],["dc.relation.eventlocation","Edinburgh, Scotland"],["dc.title","SIRT2 as a genetic modifier of axonal degeneration in white matter tracts"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e77019"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Gargareta, Vasiliki-Ilya"],["dc.contributor.author","Reuschenbach, Josefine"],["dc.contributor.author","Siems, Sophie B"],["dc.contributor.author","Sun, Ting"],["dc.contributor.author","Piepkorn, Lars"],["dc.contributor.author","Mangana, Carolina"],["dc.contributor.author","Späte, Erik"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Huitinga, Inge"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke B"],["dc.date.accessioned","2022-06-01T09:40:04Z"],["dc.date.available","2022-06-01T09:40:04Z"],["dc.date.issued","2022"],["dc.description.abstract","Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here, we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP, and SEPTIN8 correlates well with that in C57Bl/6N mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein 2 (PMP2), which was specific to human central nervous system myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes, including Pmp2, Tspan2, and Gjc3 . A searchable web interface is accessible via www.mpinat.mpg.de/myelin . Species-dependent diversity of oligodendroglial mRNA expression and myelin protein composition can be informative when translating from mouse models to humans."],["dc.description.abstract","Like the electrical wires in our homes, the processes of nerve cells – the axons, thin extensions that project from the cell bodies – need to be insulated to work effectively. This insulation takes the form of layers of a membrane called myelin, which is made of proteins and fats and produced by specialized cells called oligodendrocytes in the brain and the spinal cord. If this layer of insulation becomes damaged, the electrical impulses travelling along the nerves slow down, affecting the ability to walk, speak, see or think. This is the cause of several illnesses, including multiple sclerosis and a group of rare genetic diseases known as leukodystrophies. A lot of the research into myelin, oligodendrocytes and the diseases caused by myelin damage uses mice as an experimental model for humans. Using mice for this type of research is appropriate because of the ethical and technical limitations of experiments on humans. This approach can be highly effective because mice and humans share a large proportion of their genes. However, there are many obvious physical differences between the two species, making it important to determine whether the results of experiments performed in mice are applicable to humans. To do this, it is necessary to understand how myelin differs between these two species at the molecular level. Gargareta, Reuschenbach, Siems, Sun et al. approached this problem by studying the proteins found in myelin isolated from the brains of people who had passed away and donated their organs for scientific research. They used a technique called mass spectrometry, which identifies molecules based on their weight, to produce a list of proteins in human myelin that could then be compared to existing data from mouse myelin. This analysis showed that myelin is very similar in both species, but some proteins only appear in humans or in mice. Gargareta, Reuschenbach, Siems, Sun et al. then compared which genes are turned on in the oligodendrocytes making the myelin. The results of this comparison reflected most of the differences and similarities seen in the myelin proteins. Despite the similarities identified by Gargareta, Reuschenbach, Siems, Sun et al., it became evident that there are unexpected differences between the myelin of humans and mice that will need to be considered when applying results from mice research to humans. To enable this endeavor, Gargareta, Reuschenbach, Siems, Sun et al. have created a searchable web interface of the proteins in myelin and the genes expressed in oligodendrocytes in the two species."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship"," European Research Council"],["dc.identifier.doi","10.7554/eLife.77019"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108629"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","2050-084X"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S1047847720300587"],["dc.bibliographiccitation.firstpage","107492"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Structural Biology"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Möbius, Wiebke"],["dc.date.accessioned","2022-03-01T11:45:16Z"],["dc.date.available","2022-03-01T11:45:16Z"],["dc.date.issued","2020"],["dc.description.abstract","Advances in electron microscopy including improved imaging techniques and state-of-the-art detectors facilitate imaging of larger tissue volumes with electron microscopic resolution. In combination with genetic tools for the generation of mouse mutants this allows assessing the three-dimensional (3D) characteristics of pathological features in disease models. Here we revisited the axonal pathology in the central nervous system of a mouse model of spastic paraplegia type 2, the Plp−/Y mouse. Although PLP is a bona fide myelin protein, the major hallmark of the disease in both SPG2 patients and mouse models are axonal swellings comprising accumulations of numerous organelles including mitochondria, gradually leading to irreversible axonal loss. To assess the number and morphology of axonal mitochondria and the overall myelin preservation we evaluated two sample preparation techniques, chemical fixation or high-pressure freezing and freeze substitution, with respect to the objective of 3D visualization. Both methods allowed visualizing distribution and morphological details of axonal mitochondria. In Plp−/Y mice the number of mitochondria is 2-fold increased along the entire axonal length. Mitochondria are also found in the excessive organelle accumulations within axonal swellings. In addition, organelle accumulations were detected within the myelin sheath and the inner tongue. We find that 3D electron microscopy is required for a comprehensive understanding of the size, content and frequency of axonal swellings, the hallmarks of axonal pathology."],["dc.identifier.doi","10.1016/j.jsb.2020.107492"],["dc.identifier.pii","S1047847720300587"],["dc.identifier.pmid","32156581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103268"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/23"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | P08: Strukturelle und funktionale Veränderungen der inneren mitochondrialen Membran axonaler Mitochondrien in vivo in einem dymyelinisierenden Mausmodell"],["dc.relation.issn","1047-8477"],["dc.relation.workinggroup","RG Möbius"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Pathology of myelinated axons in the PLP-deficient mouse model of spastic paraplegia type 2 revealed by volume imaging using focused ion beam-scanning electron microscopy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1832"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1847"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","de Monasterio-Schrader, Patricia"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Barrette, Benoit"],["dc.contributor.author","Wagner, Tadzio L."],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Edgar, Julia M."],["dc.contributor.author","Brophy, Peter J."],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2022-03-01T11:45:36Z"],["dc.date.available","2022-03-01T11:45:36Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1002/glia.22561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103390"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0894-1491"],["dc.title","Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin-2"],["dc.title.alternative","Tspan2-Deficient Myelin Induces Neuroinflammation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6586"],["dc.bibliographiccitation.issue","29"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","6596"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Heibeck, Saskia"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","tom Dieck, Susanne"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Salditt, Tim"],["dc.contributor.author","Rodicio, María C."],["dc.contributor.author","Morgan, Jennifer R."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2020-12-10T18:42:35Z"],["dc.date.available","2020-12-10T18:42:35Z"],["dc.date.issued","2018"],["dc.description.abstract","In the nervous system, myelination of axons enables rapid impulse conduction and is a specialized function of glial cells. Myelinating glia are the last cell type to emerge in the evolution of vertebrate nervous systems, presumably in ancient jawed vertebrates (gnathostomata) because jawless vertebrates (agnathans) lack myelin. We have hypothesized that, in these unmyelinated species, evolutionary progenitors of myelinating cells must have existed that should still be present in contemporary agnathan species. Here, we used advanced electron microscopic techniques to reveal axon-glia interactions in the sea lamprey Petromyzon marinus By quantitative assessment of the spinal cord and the peripheral lateral line nerve, we observed a marked maturation-dependent growth of axonal calibers. In peripheral nerves, all axons are ensheathed by glial cells either in bundles or, when larger than the threshold caliber of 3 μm, individually. The ensheathing glia are covered by a basal lamina and express SoxE-transcription factors, features of mammalian Remak-type Schwann cells. In larval lamprey, the ensheathment of peripheral axons leaves gaps that are closed in adults. CNS axons are also covered to a considerable extent by glial processes, which contain a high density of intermediate filaments, glycogen particles, large lipid droplets, and desmosomes, similar to mammalian astrocytes. Indeed, by in situ hybridization, these glial cells express the astrocyte marker Aldh1l1 Specimens were of unknown sex. Our observations imply that radial sorting, ensheathment, and presumably also metabolic support of axons are ancient functions of glial cells that predate the evolutionary emergence of myelin in jawed vertebrates.SIGNIFICANCE STATEMENT We used current electron microscopy techniques to examine axon-glia units in a nonmyelinated vertebrate species, the sea lamprey. In the PNS, lamprey axons are fully ensheathed either individually or in bundles by cells ortholog to Schwann cells. In the CNS, axons associate with astrocyte orthologs, which contain glycogen and lipid droplets. We suggest that ensheathment, radial sorting, and metabolic support of axons by glial cells predate the evolutionary emergence of myelin in ancient jawed vertebrates."],["dc.identifier.doi","10.1523/JNEUROSCI.1034-18.2018"],["dc.identifier.eissn","1529-2401"],["dc.identifier.issn","0270-6474"],["dc.identifier.pmid","29941446"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78012"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.eissn","1529-2401"],["dc.relation.issn","0270-6474"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.subject.gro","biomedical tomography"],["dc.title","Axonal Ensheathment in the Nervous System of Lamprey: Implications for the Evolution of Myelinating Glia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cell and Developmental Biology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Siems, Sophie B."],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Hoodless, Laura J."],["dc.contributor.author","Jung, Ramona B."],["dc.contributor.author","Hesse, Dörte"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Czopka, Tim"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2022-03-01T11:44:21Z"],["dc.date.available","2022-03-01T11:44:21Z"],["dc.date.issued","2021"],["dc.description.abstract","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."],["dc.description.abstract","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."],["dc.identifier.doi","10.3389/fcell.2021.640169"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103004"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","2296-634X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Proteome Profile of Myelin in the Zebrafish Brain"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]