Myelin‐associated oligodendrocytic basic protein is essential for normal arrangement of the radial component in central nervous system myelin

Yamamoto, Yoichi; Yoshikawa, Hiroaki; Nagano, Seiichi; Kondoh, Gen; Sadahiro, Shigeki; Gotow, Takahiro; Yanagihara, Takehiko; Sakoda, Saburo

doi:10.1046/j.1460-9568.1999.00490.x

Cited by 48 publications

(42 citation statements)

References 40 publications

(75 reference statements)

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“…Despite the strong morphological effects we observed in oligodendrocytes upon the manipulation of MOBP levels, it is surprising that the absence of MOBP in vivo still allows the synthesis of relatively normal myelin (Yamamoto et al, 1999;Yool et al, 2002). However, the absence of MOBP results in an abnormally arranged radial component and the compact myelin appears to be less stable, as exposure to the dysmyelinating hexachlorophene results in a widened major dense line in MOBPknockout mice (Yamamoto et al, 1999;Yoshikawa, 2001). It has therefore been postulated that MOBP plays a role in the maintenance of compact myelin rather than being required for its synthesis.…”

Section: Mobp and Oligodendroglial Morphological Differentiationmentioning

confidence: 81%

“…The C-termini of the larger MOBP isoforms do not seem to interact with membranes and have been proposed to be located in the small cytoplasmic space of the major dense line in compacted myelin (Myllykoski et al, 2012). Despite the strong morphological effects we observed in oligodendrocytes upon the manipulation of MOBP levels, it is surprising that the absence of MOBP in vivo still allows the synthesis of relatively normal myelin (Yamamoto et al, 1999;Yool et al, 2002). However, the absence of MOBP results in an abnormally arranged radial component and the compact myelin appears to be less stable, as exposure to the dysmyelinating hexachlorophene results in a widened major dense line in MOBPknockout mice (Yamamoto et al, 1999;Yoshikawa, 2001).…”

Section: Mobp and Oligodendroglial Morphological Differentiationmentioning

confidence: 82%

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MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

Schäfer

Müller

Luhmann

et al. 2016

Journal of Cell Science

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Oligodendrocytes are the myelinating glial cells of the central nervous system (CNS). Myelin is formed by extensive wrapping of oligodendroglial processes around axonal segments, which ultimately allows a rapid saltatory conduction of action potentials within the CNS and sustains neuronal health. The non-receptor tyrosine kinase Fyn is an important signaling molecule in oligodendrocytes. It controls the morphological differentiation of oligodendrocytes and is an integrator of axon-glial signaling cascades leading to localized synthesis of myelin basic protein (MBP), which is essential for myelin formation. The abundant myelinassociated oligodendrocytic basic protein (MOBP) resembles MBP in several aspects and has also been reported to be localized as mRNA and translated in the peripheral myelin compartment. The signals initiating local MOBP synthesis are so far unknown and the cellular function of MOBP remains elusive. Here, we show, by several approaches in cultured primary oligodendrocytes, that MOBP synthesis is stimulated by Fyn activity. Moreover, we reveal a new function for MOBP in oligodendroglial morphological differentiation.

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Section: Mobp and Oligodendroglial Morphological Differentiationmentioning

confidence: 81%

Section: Mobp and Oligodendroglial Morphological Differentiationmentioning

confidence: 82%

MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

Schäfer

Müller

Luhmann

et al. 2016

Journal of Cell Science

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“…It has been proposed that MOBP has an intimate role in the stabilization of the radial component characterized by a band of claudin-/oligodendrocyte-specifi c protein (OSP)-rich tight junctions crossing the myelin sheath [23,24] . However, despite signifi cant effort, the function of MOBP per se or any of the individual isoforms remains unclear.…”

Section: Mobp Is a Component Of The Major Dense Line Of Cns Myelinmentioning

confidence: 99%

“…Two Mobp -null mice have been described [11,23] . The mutation in the line reported by us [11] results in the loss of all MOBP isoforms, including MOBP155 ( fi g. 1 a).…”

Section: Phenotypic Analysis Of Mobp-null Strainsmentioning

confidence: 99%

Myelin-Associated Oligodendrocytic Basic Protein: A Family of Abundant CNS Myelin Proteins in Search of a Function

et al. 2006

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The myelin-associated oligodendrocytic basic protein (MOBP) family constitutes the third most abundant protein in CNS myelin. The mouse Mobp gene comprises eight exons. Mobp pre-mRNA processing gives rise to at least seven Mobp splice variants which are expressed solely in the oligodendrocyte. The predicted proteins all, with one exception, share a 68 residue amino terminus, encoded by exon 3. The carboxyl termini differ in length, giving rise to the diverse array of the protein isoforms. Like myelin basic protein, MOBP is present in the major dense line of CNS myelin suggesting a role in the compaction or stabilization of myelin. However, Mobp homozygous null mice display no overt clinical phenotype and no defect in the process of myelination. MOBP can induce experimental allergic encephalomyelitis in mice and has been proposed to have a role in the pathogenesis of multiple sclerosis. Despite 10 years of rigorous study, the normal physiological function of MOBP remains unknown.

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“…MOBP, a CNS myelin-specific protein thought to play a role in stabilizing the myelin sheath (15)(16)(17), was recently shown to be encephalitogenic. Thus, active immunization with recombinant preparations of both the long (rOPRP1) and the short (MOBP81) MOBP isoforms could induce EAE in BALB/c (H-2 d ) and/or SJL/J (H-2 s ) mice (1).…”

mentioning

confidence: 99%

The Myelin-Associated Oligodendrocytic Basic Protein Region MOBP15–36 Encompasses the Immunodominant Major Encephalitogenic Epitope(s) for SJL/J Mice and Predicted Epitope(s) for Multiple Sclerosis-Associated HLA-DRB1*1501

Rosbo¹,

Kaye²,

Eisenstein

et al. 2004

The Journal of Immunology

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Autoimmune response to the myelin-associated oligodendrocytic basic protein (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune response to MOBP and the associated pathology in the CNS have not yet been fully investigated. In this study, we have characterized the clinical manifestations, pathology, T cell epitope-specificity, and TCRs associated with experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells for reactivity to overlapping MOBP peptides defined MOBP15–36 as their major immunodominant epitope. Accordingly, MOBP15–36 was demonstrated to be the major encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical EAE associated with intense perivascular and parenchymal infiltrations, widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular modeling of the interaction of I-As with MOBP15–36, together with analysis of the MOBP15–36-specific T cell response to truncated peptides, suggests MOBP20–28 as the core sequence for I-As-restricted recognition of the encephalitogenic region MOBP15–36. Although highly focused in their epitope specificity, the encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vβ genes. These results would therefore favor epitope-directed, rather than TCR-targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity. Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP epitope within the encephalitogenic MOBP15–36 sequence suggests the potential relevance of T cell reactivity against MOBP15–36 to MS. The reactivity to MOBP15–36 detected in MS shown here and in another study further emphasizes the potential significance of this epitope for MS.

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Myelin‐associated oligodendrocytic basic protein is essential for normal arrangement of the radial component in central nervous system myelin

Cited by 48 publications

References 40 publications

MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

Myelin-Associated Oligodendrocytic Basic Protein: A Family of Abundant CNS Myelin Proteins in Search of a Function

The Myelin-Associated Oligodendrocytic Basic Protein Region MOBP15–36 Encompasses the Immunodominant Major Encephalitogenic Epitope(s) for SJL/J Mice and Predicted Epitope(s) for Multiple Sclerosis-Associated HLA-DRB1*1501

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