Werner, Hauke B.

[["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","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.journal","eLife"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Erwig, Michelle S"],["dc.contributor.author","Tenzer, Stefan"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Schaeren-Wiemers, Nicole"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Werner, Hauke B"],["dc.date.accessioned","2021-06-01T10:48:59Z"],["dc.date.available","2021-06-01T10:48:59Z"],["dc.date.issued","2016"],["dc.description.abstract","Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confocal microscopy and immunogold-electron microscopy, these filaments are localized to the non-compacted adaxonal myelin compartment. Genetic disruption of these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific neuropathology. Septin filaments thus serve an important function in scaffolding the axon/myelin-unit, evidently a late stage of myelin maturation. We propose that pathological or aging-associated diminishment of the septin/anillin-scaffold causes myelin outfoldings that impair the normal nerve conduction velocity."],["dc.description.abstract","Normal communication within the brain or between the brain and other parts of the body requires information to flow quickly around the nervous system. This information travels along nerve cells in the form of electrical signals. To speed up the signals, a part of the nerve cell called the axon is frequently wrapped in an electrically insulating sheath made up of a membrane structure called myelin. The myelin sheath becomes impaired as a result of disease or ageing. In order to understand what might produce these changes, Patzig et al. have used biochemical and microscopy techniques to study mice that had similar defects in their myelin sheaths. The study reveals that forming a normal myelin sheath around an axon requires a newly identified ‘scaffold’ made of a group of proteins called the septins. Combining with another protein called anillin, septins assemble into filaments in the myelin sheath. These filaments then knit together into a scaffold that grows lengthways along the myelin-wrapped axon. Without this scaffold, the myelin sheath grew defects known as outfoldings. Axons transmitted electrical signals much more slowly than normal when the septin scaffold was missing from the myelin sheath. Future studies are needed to understand the factors that control how the septin scaffold forms. This could help to reveal ways of reversing the changes that alter the myelin sheath during ageing and disease."],["dc.identifier.doi","10.7554/eLife.17119"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13756"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86124"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2050-084X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e254"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Klugmann, M."],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Monasterio-Schrader, P. D."],["dc.contributor.author","Strenzke, N."],["dc.contributor.author","Flügge, G."],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Pawlak, R."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:37Z"],["dc.date.available","2017-09-07T11:46:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia."],["dc.format.extent","12"],["dc.identifier.doi","10.1038/tp.2013.28"],["dc.identifier.gro","3150562"],["dc.identifier.pmid","23632458"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10616"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7336"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject","chromosome 4; GPM6A; human pedigree; miR124; mouse mutant; panic disorder"],["dc.title","A single gene defect causing claustrophobia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","155"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","174"],["dc.bibliographiccitation.volume","64"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Eichel, Maria A."],["dc.contributor.author","Lueders, Katja A."],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Martini, Rudolf"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2018-11-07T10:21:33Z"],["dc.date.available","2018-11-07T10:21:33Z"],["dc.date.issued","2016"],["dc.description.abstract","Protein zero (P0) is the major structural component of peripheral myelin. Lack of this adhesion protein from Schwann cells causes a severe dysmyelinating neuropathy with secondary axonal degeneration in humans with the neuropathy Dejerine-Sottas syndrome (DSS) and in the corresponding mouse model (P0(null)-mice). In the mammalian CNS, the tetraspan-membrane protein PLP is the major structural myelin constituent and required for the long-term preservation of myelinated axons, which fails in hereditary spastic paraplegia (SPG type-2) and the relevant mouse model (Plp(null)-mice). The Plp-gene is also expressed in Schwann cells but PLP is of very low abundance in normal peripheral myelin; its function has thus remained enigmatic. Here we show that the abundance of PLP but not of other tetraspan myelin proteins is strongly increased in compact peripheral myelin of P0(null)-mice. To determine the functional relevance of PLP expression in the absence of P0, we generated P0(null star) Plp(null)-double-mutant mice. Compared with either single-mutant, P0(null star) Plp(null)-mice display impaired nerve conduction, reduced motor functions, and premature death. At the morphological level, axonal segments were frequently non-myelinated but in a one-to-one relationship with a hypertrophic Schwann cell. Importantly, axonal numbers were reduced in the vital phrenic nerve of P0(null star) Plp(null)-mice. In the absence of P0, thus, PLP also contributes to myelination by Schwann cells and to the preservation of peripheral axons. These data provide a link between the Schwann cell-dependent support of peripheral axons and the oligodendrocyte-dependent support of central axons."],["dc.identifier.doi","10.1002/glia.22922"],["dc.identifier.isi","000367677600011"],["dc.identifier.pmid","26393339"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42116"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Proteolipid Protein Modulates Preservation of Peripheral Axons and Premature Death when Myelin Protein Zero is Lacking"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","cm.21736"],["dc.bibliographiccitation.journal","Cytoskeleton"],["dc.contributor.author","Martens, Ann‐Kristin"],["dc.contributor.author","Erwig, Michelle"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Füchtbauer, Ernst‐Martin"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2022-12-01T08:30:39Z"],["dc.date.available","2022-12-01T08:30:39Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/cm.21736"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117943"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1949-3592"],["dc.relation.issn","1949-3584"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc/4.0/"],["dc.title","Targeted inactivation of the\n Septin2\n and\n Septin9\n genes in myelinating Schwann cells of mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Erwig, Michelle S."],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Heilmann, Mareike"],["dc.contributor.author","Heilmann, Ingo"],["dc.contributor.author","Jung, Ramona B."],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2019-08-02T06:29:41Z"],["dc.date.available","2019-08-02T06:29:41Z"],["dc.date.issued","2019"],["dc.description.abstract","Myelin serves as an axonal insulator that facilitates rapid nerve conduction along axons. By transmission electron microscopy, a healthy myelin sheath comprises compacted membrane layers spiraling around the cross-sectioned axon. Previously we identified the assembly of septin filaments in the innermost non-compacted myelin layer as one of the latest steps of myelin maturation in the central nervous system (CNS) (Patzig et al., 2016). Here we show that loss of the cytoskeletal adaptor protein anillin (ANLN) from oligodendrocytes disrupts myelin septin assembly, thereby causing the emergence of pathological myelin outfoldings. Since myelin outfoldings are a poorly understood hallmark of myelin disease and brain aging we assessed axon/myelin-units in Anln-mutant mice by focused ion beam-scanning electron microscopy (FIB-SEM); myelin outfoldings were three-dimensionally reconstructed as large sheets of multiple compact membrane layers. We suggest that anillin-dependent assembly of septin filaments scaffolds mature myelin sheaths, facilitating rapid nerve conduction in the healthy CNS."],["dc.identifier.doi","10.7554/eLife.43888"],["dc.identifier.pmid","30672734"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15932"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62262"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","2050-084X"],["dc.relation.issn","2050-084X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Anillin facilitates septin assembly to prevent pathological outfoldings of central nervous system myelin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","634"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","649"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Lüders, Katja A."],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Jung, Ramona B."],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2022-03-01T11:45:39Z"],["dc.date.available","2022-03-01T11:45:39Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1002/glia.23549"],["dc.identifier.issn","0894-1491"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103401"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0894-1491"],["dc.title","Maintenance of high proteolipid protein level in adult central nervous system myelin is required to preserve the integrity of myelin and axons"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","254"],["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.lastpage","263"],["dc.bibliographiccitation.volume","277"],["dc.contributor.author","Dere, Ekrem"],["dc.contributor.author","Winkler, Daniela"],["dc.contributor.author","Ritter, Caroline"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Poggi, Giulia"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Gernert, Manuela"],["dc.contributor.author","Müller, Christian"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Werner, Hauke B."],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2015"],["dc.description.abstract","The neuronal tetraspan proteins, M6A (Gpm6a) and M6B (Gpm6b), belong to the family of proteolipids that are widely expressed in the brain. We recently reported Gpm6a deficiency as a monogenetic cause of claustrophobia in mice. Its homolog proteolipid, Gpm6b, is ubiquitously expressed in neurons and oligodendrocytes. Gpm6b is involved in neuronal differentiation and myelination. It interacts with the N-terminal domain of the serotonin transporter (SERT) and decreases cell-surface expression of SERT. In the present study, we employed Gpm6b null mutant mice (Gpm6b(-/-)) to search for behavioral functions of Gpm6b. We studied male and female Gpm6b(-/-) mice and their wild-type (WT, Gpm6b(+/+)) littermates in an extensive behavioral test battery. Additionally, we investigated whether Gpm6b(-/-) mice exhibit changes in the behavioral response to a 5-HT2A/C receptor agonist. We found that Gpm6b(-/-) mice display completely normal sensory and motor functions, cognition, as well as social and emotionality-like (anxiety, depression) behaviors. On top of this inconspicuous behavioral profile, Gpm6b(-/-) mice of both genders exhibit a selective impairment in prepulse inhibition of the acoustic startle response. Furthermore, in contrast to WT mice that show the typical locomotion suppression and increase in grooming activity after intraperitoneal administration of DOI [(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride], Gpm6b(-/-) mice demonstrate a blunted behavioral response to this 5-HT2A/C receptor agonist. To conclude, Gpm6b deficiency impairs sensorimotor gating and modulates the behavioral response to a serotonergic challenge."],["dc.identifier.doi","10.1016/j.bbr.2014.04.021"],["dc.identifier.gro","3150542"],["dc.identifier.pmid","24768641"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7315"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.subject","Glycoprotein M6B; Prepulse inhibition; Serotonin transporter (SERT); Proteolipid protein (PLP); Gpm6a; C57BL/6J"],["dc.title","Gpm6b deficiency impairs sensorimotor gating and modulates the behavioral response to a 5-HT2A/C receptor agonist"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]