scholarly journals Schwann Cell Myelination Requires Timely and Precise Targeting of P0 Protein

2000 ◽  
Vol 148 (5) ◽  
pp. 1009-1020 ◽  
Author(s):  
X. Yin ◽  
G.J. Kidd ◽  
L. Wrabetz ◽  
M.L. Feltri ◽  
A. Messing ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Structural Protein ◽  
Major Structural Protein ◽  
Adult Mice ◽  
Pns Myelin ◽  
P0 Protein ◽  
Dynamic Membranes ◽  
Myelin Associated Glycoprotein ◽  
Homophilic Adhesion

This report investigated mechanisms responsible for failed Schwann cell myelination in mice that overexpress P0 (P0tg), the major structural protein of PNS myelin. Quantitative ultrastructural immunocytochemistry established that P0 protein was mistargeted to abaxonal, periaxonal, and mesaxon membranes in P0tg Schwann cells with arrested myelination. The extracellular leaflets of P0-containing mesaxon membranes were closely apposed with periodicities of compact myelin. The myelin-associated glycoprotein was appropriately sorted in the Golgi apparatus and targeted to periaxonal membranes. In adult mice, occasional Schwann cells myelinated axons possibly with the aid of endocytic removal of mistargeted P0. These results indicate that P0 gene multiplication causes P0 mistargeting to mesaxon membranes, and through obligate P0 homophilic adhesion, renders these dynamic membranes inert and halts myelination.

scholarly journals Distribution of the myelin-associated glycoprotein and P0 protein during myelin compaction in quaking mouse peripheral nerve.

1988 ◽  
Vol 107 (2) ◽  
pp. 675-685 ◽  
Author(s):  
B D Trapp
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Mouse Mutant ◽  
Structural Protein ◽  
Major Structural Protein ◽  
Ultrastructural Studies ◽  
P0 Protein ◽  
Myelin Associated Glycoprotein ◽  
Ventral Roots ◽  
Quaking Mice

Ultrastructural studies have shown that during early stages of Schwann cell myelination mesaxon membranes are converted to compact myelin lamellae. The distinct changes that occur in the spacing of these Schwann cell membranes are likely to be mediated by the redistribution of (a) the myelin-associated glycoprotein, a major structural protein of mesaxon membranes; and (b) P0 protein, the major structural protein of compact myelin. To test this hypothesis, the immunocytochemical distribution of these two proteins was determined in serial 1-micron-thick Epon sections of ventral roots from quaking mice and compared to the ultrastructure of identical areas in an adjacent thin section. Ventral roots of this hypomyelinating mouse mutant were studied because many fibers have a deficit in converting mesaxon membranes to compact myelin. The results indicated that conversion of mesaxon membranes to compact myelin involves the insertion of P0 protein into and the removal of the myelin-associated glycoprotein from mesaxon membranes. The failure of some quaking mouse Schwann cells to form compact myelin appears to result from an inability to remove the myelin-associated glycoprotein from their mesaxon membranes.

scholarly journals Myelin-associated glycoprotein and myelinating Schwann cell-axon interaction in chronic B,B'-iminodipropionitrile neuropathy.

1984 ◽  
Vol 98 (4) ◽  
pp. 1272-1278 ◽  
Author(s):  
B D Trapp ◽  
R H Quarles ◽  
J W Griffin
Keyword(s):  
Schwann Cell ◽  
Central Zone ◽  
Minor Component ◽  
Outer Zone ◽  
Structural Protein ◽  
Myelinated Fibers ◽  
Pns Myelin ◽  
Myelin Associated Glycoprotein ◽  
Myelinating Schwann Cell ◽  
Periaxonal Space

The myelin-associated glycoprotein (MAG) is a heavily glycosylated integral membrane glycoprotein which is a minor component of isolated rat peripheral nervous system (PNS) myelin. Immunocytochemically MAG has been localized in the periaxonal region of PNS myelin sheaths. The periaxonal localization and biochemical features of MAG are consistent with the hypothesis that MAG plays a role in maintaining the periaxonal space of myelinated fibers. To test this hypothesis, MAG was localized immunocytochemically in 1-micron sections of the L5 ventral root from rats exposed to B,B'-iminodipropionitrile. In chronic states of B,B'-iminodipropionitrile intoxication, Schwann cell periaxonal membranes and the axolemma invaginate into giant axonal swellings and separate a central zone of normally oriented axoplasm from an outer zone of maloriented neurofilaments. Ultrastructurally, the width of the periaxonal space (12-14 nm) in the ingrowths is identical to that found in normally myelinated fibers. These Schwann cell ingrowths which are separated from compact myelin by several micra are stained intensely by MAG antiserum. Antiserum directed against Po protein, the major structural protein of compact PNS myelin, does not stain the ingrowths unless compact myelin is present. These results demonstrate the periaxonal localization of MAG and support a functional role for MAG in maintaining the periaxonal space of PNS myelinated fibers.

scholarly journals Presence of the myelin-associated glycoprotein correlates with alterations in the periodicity of peripheral myelin.

1982 ◽  
Vol 92 (3) ◽  
pp. 877-882 ◽  
Author(s):  
B D Trapp ◽  
R H Quarles
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerves ◽  
Minor Component ◽  
Integral Membrane Protein ◽  
Structural Protein ◽  
Adult Rat ◽  
Pns Myelin ◽  
Myelin Associated Glycoprotein ◽  
A Minor ◽  
Periaxonal Space

The myelin-associated glycoprotein (MAG) is an integral membrane protein (congruent to 100,000 mol wt) which is a minor component of purified peripheral nervus system (PNS) myelin. In the present study, MAG was localized immunocytochemically in 1-micrometer thick Epon sections of 7-d and adult rat peripheral nerves, and its localization was compared to that of the major structural protein (Po) of PNS myelin. To determine more precisely the localization of MAG, immunostained areas in 1 micrometer sections were traced on electron micrographs of identical areas from adjacently cut thin sections.l MAG was localized in periaxonal membranes. Schmidt-Lantermann incisures, paranodal membranes, and the outer mesaxon of PNS myelin sheaths. Compact regions of PNS myelin did not react with MAG antiserum. The results demonstrate MAG's presence in "'semi-compact" Schwann cell or myelin membranes that have a gap of 12-14 nm between extracellular leaflets and a spacing of 5 nm or more between cytoplasmic leaflets. In compact regions of the myelin sheath which do not contain MAG, the cytoplasmic leaflets are "fused" and form the major dense line, whereas the extracellular leaflets are separated by a 2.0 nm gap appearing as paired minor dense lines. Thus, it is proposed that MAG plays a role in maintaining the periaxonal space, Schmidt-Lantermann incisures, paranodal myelin loops, and outer mesaxon by preventing "complete" compaction of Schwann cell and myelin membranes. The presence of MAG in these locations also suggests that MAG may serve a function in regulating myelination in the PNS.

scholarly journals Immortalized Adult Rodent Schwann Cells as In Vitro Models to Study Diabetic Neuropathy

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kazunori Sango ◽  
Hiroko Yanagisawa ◽  
Shizuka Takaku ◽  
Emiko Kawakami ◽  
Kazuhiko Watabe
Keyword(s):  
Schwann Cell ◽  
Diabetic Neuropathy ◽  
Schwann Cells ◽  
Cell Lines ◽  
Polyol Pathway ◽  
Mouse Cell ◽  
Biological Properties ◽  
In Vitro Models ◽  
Adult Mice

We have established spontaneously immortalized Schwann cell lines from normal adult mice and rats and murine disease models. One of the normal mouse cell lines, IMS32, possesses some biological properties of mature Schwann cells and high proliferative activities. The IMS32 cells under hyperglycemic and/or hyperlipidemic conditions have been utilized to investigate the pathogenesis of diabetic neuropathy, especially the polyol pathway hyperactivity, glycation, increased oxidative stress, and reduced synthesis of neurotrophic factors. In addition to the mouse cell lines, our current study focuses on the characterization of a normal rat cell line, IFRS1, under normal and high glucose conditions. These Schwann cell lines can be valuable tools for exploring the detailed mechanisms leading to diabetic neuropathy and novel therapeutic approaches against that condition.

scholarly journals Immunocytochemical studies of quaking mice support a role for the myelin-associated glycoprotein in forming and maintaining the periaxonal space and periaxonal cytoplasmic collar of myelinating Schwann cells.

1984 ◽  
Vol 99 (2) ◽  
pp. 594-606 ◽  
Author(s):  
B D Trapp ◽  
R H Quarles ◽  
K Suzuki
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Plasma Membranes ◽  
Immunocytochemical Localization ◽  
Myelinated Fibers ◽  
Cell Plasma ◽  
Myelin Associated Glycoprotein ◽  
Quaking Mice ◽  
Periaxonal Space ◽  
Cytoplasmic Side

The myelin-associated glycoprotein (MAG) is an integral membrane glycoprotein that is located in the periaxonal membrane of myelin-forming Schwann cells. On the basis of this localization, it has been hypothesized that MAG plays a structural role in (a) forming and maintaining contact between myelinating Schwann cells and the axon (the 12-14-nm periaxonal space) and (b) maintaining the Schwann cell periaxonal cytoplasmic collar of myelinated fibers. To test this hypothesis, we have determined the immunocytochemical localization of MAG in the L4 ventral roots from 11-mo-old quaking mice. These roots display various stages in the association of remyelinating Schwann cells with axons, and abnormalities including loss of the Schwann cell periaxonal cytoplasmic collar and dilation of the periaxonal space of myelinated fibers. Therefore, this mutant provides distinct opportunities to observe the relationships between MAG and (a) the formation of the periaxonal space during remyelination and (b) the maintenance of the periaxonal space and Schwann cell periaxonal cytoplasmic collar in myelinated fibers. During association of remyelinating Schwann cells and axons, MAG was detected in Schwann cell adaxonal membranes that apposed the axolemma by 12-14 nm. Schwann cell plasma membranes separated from the axolemma by distances greater than 12-14 nm did not react with MAG antiserum. MAG was present in adaxonal Schwann cell membranes that apposed the axolemma by 12-14 nm but only partially surrounded the axon and, therefore, may be actively involved in the ensheathment of axons by remyelinating Schwann cells. To test the dual role of MAG in maintaining the periaxonal space and Schwann cell periaxonal cytoplasmic collar of myelinated fibers, we determined the immunocytochemical localization of MAG in myelinated quaking fibers that displayed pathological alterations of these structures. Where Schwann cell periaxonal membranes were not stained by MAG antiserum, the cytoplasmic side of the periaxonal membrane was "fused" with the cytoplasmic side of the inner compact myelin lamella and formed a major dense line. This loss of MAG and the Schwann cell periaxonal cytoplasmic collar usually resulted in enlargement of the 12-14-nm periaxonal space and ruffling of the apposing axolemma. In myelinated fibers, there was a strict correlation between the presence of MAG in the Schwann cell periaxonal membrane and (a) maintenance of the 12-14-nm periaxonal space, and (b) presence of the Schwann cell periaxonal cytoplasmic collar.(ABSTRACT TRUNCATED AT 400 WORDS)

Expressing antisense P0 RNA in Schwann cells perturbs myelination

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 639-649
Author(s):  
G.C. Owens ◽  
C.J. Boyd
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Dorsal Root Ganglion Neurons ◽  
Beta Actin ◽  
Actin Promoter ◽  
Dominant Selectable Marker ◽  
Myelin Associated Glycoprotein ◽  
Ganglion Neurons ◽  
Schwann Cell Differentiation

Primary Schwann cells were infected in vitro with a recombinant retrovirus expressing a dominant selectable marker, neomycin phosphotransferase (conferring resistance to the drug G418), and antisense P0 RNA under the control of the human beta-actin promoter. A proportion of the G418-resistant cells failed to form myelin when cocultured with dorsal root ganglion neurons under conditions that promote Schwann cell differentiation. These cells expressed high levels of P0 antisense RNA. Among the impaired cells, the majority had segregated and ensheathed individual axon but had not differentiated further. They did not express P0 but did express myelin- associated glycoprotein and galactocerebroside. A minority of partially inhibited Schwann cells were also observed that elaborated thin myelin sheaths containing variable numbers of compacted and noncompacted lamellae. These data indicate that restricting the level of P0 expression inhibits spiralling of the Schwann cell membrane and subsequent compaction.

scholarly journals Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination.

1993 ◽  
Vol 123 (5) ◽  
pp. 1223-1236 ◽  
Author(s):  
S Einheber ◽  
T A Milner ◽  
F Giancotti ◽  
J L Salzer
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cell Contact ◽  
Myelin Associated Glycoprotein ◽  
Dorsal Root Ganglia Neurons ◽  
Outer Plasma Membrane

Ensheathment and myelination of axons by Schwann cells in the peripheral nervous system requires contact with a basal lamina. The molecular mechanism(s) by which the basal lamina promotes myelination is not known but is likely to reflect the activity of integrins expressed by Schwann cells. To initiate studies on the role of integrins during myelination, we characterized the expression of two integrin subunits, beta 1 and beta 4, in an in vitro myelination system and compared their expression to that of the glial adhesion molecule, the myelin-associated glycoprotein (MAG). In the absence of neurons, Schwann cells express significant levels of beta 1 but virtually no beta 4 or MAG. When Schwann cells are cocultured with dorsal root ganglia neurons under conditions promoting myelination, expression of beta 4 and MAG increased dramatically in myelinating cells, whereas beta 1 levels remained essentially unchanged. (In general agreement with these findings, during peripheral nerve development in vivo, beta 4 levels also increase during the period of myelination in sharp contrast to beta 1 levels which show a striking decrease.) In cocultures of neurons and Schwann cells, beta 4 and MAG appear to colocalize in nascent myelin sheaths but have distinct distributions in mature sheaths, with beta 4 concentrated in the outer plasma membrane of the Schwann cell and MAG localized to the inner (periaxonal) membrane. Surprisingly, beta 4 is also present at high levels with MAG in Schmidt-Lanterman incisures. Immunoprecipitation studies demonstrated that primary Schwann cells express beta 1 in association with the alpha 1 and alpha 6 subunits, while myelinating Schwann cells express alpha 6 beta 4 and possibly alpha 1 beta 1. beta 4 is also downregulated during Wallerian degeneration in vitro, indicating that its expression requires continuous Schwann cell contact with the axon. These results indicate that axonal contact induces the expression of beta 4 during Schwann cell myelination and suggest that alpha 6 beta 4 is an important mediator of the interactions of myelinating Schwann cells with the basal lamina.

scholarly journals Immunocytochemical localization of P0 protein in Golgi complex membranes and myelin of developing rat Schwann cells.

1981 ◽  
Vol 90 (1) ◽  
pp. 1-6 ◽  
Author(s):  
B D Trapp ◽  
Y Itoyama ◽  
N H Sternberger ◽  
R H Quarles ◽  
H Webster
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Golgi Complex ◽  
Cell Cytoplasm ◽  
Adult Rats ◽  
Thin Sections ◽  
Myelin Sheaths ◽  
Transmission Electron ◽  
P0 Protein ◽  
Developing Rat

P0 protein, the dominant protein in peripheral nervous system myelin, was studied immunocytochemically in both developing and mature Schwann cells. Trigeminal and sciatic nerves from newborn, 7-d, and adult rats were processed for transmission electron microscopy. Alternating 1-micrometer-thick Epon sections were stained with paraphenylenediamine (PD) or with P0 antiserum according to the peroxidase-antiperoxidase method. To localize P0 in Schwann cell cytoplasm and myelin membranes, the distribution of immunostaining observed in 1-micrometer sections was mapped on electron micrographs of identical areas found in adjacent thin sections. The first P0 staining was observed around axons and/or in cytoplasm of Schwann cells that had established a 1:1 relationship with axons. In newborn nerves, staining of newly formed myelin sheaths was detected more readily with P0 antiserum than with PD. Myelin sheaths with as few as three lamellae could be identified with the light microscope. Very thin sheaths often stained less intensely and part of their circumference frequently was unstained. Schmidt-Lanterman clefts found in more mature sheaths also were unstained. As myelination progressed, intensely stained myelin rings became much more numerous and, in adult nerves, all sheaths were intensely and uniformly stained. Particulate P0 staining also was observed in juxtanuclear areas of Schwann cell cytoplasm. It was most prominent during development, then decreased, but still was detected in adult nerves. The cytoplasmic areas stained by P0 antiserum were rich in Golgi complex membranes.

scholarly journals Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury

2019 ◽  
Author(s):  
Matthew Grove ◽  
Hyunkyoung Lee ◽  
Huaqing Zhao ◽  
Young-Jin Son
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Myelin Sheath ◽  
Transcriptional Activity ◽  
Axon Degeneration ◽  
Adult Mice ◽  
Functional Regeneration ◽  
Growth Promoting

ABSTRACTPreviously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.

scholarly journals The structure and organization of lanceolate mechanosensory complexes at mouse hair follicles

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Lishi Li ◽  
David D Ginty
Keyword(s):  
Schwann Cell ◽  
Hair Follicle ◽  
Schwann Cells ◽  
Hair Follicles ◽  
Electron Microscopic ◽  
Adult Mice ◽  
Hairy Skin ◽  
Cell Ablation ◽  
Low Threshold ◽  
Terminal Schwann Cells

In mouse hairy skin, lanceolate complexes associated with three types of hair follicles, guard, awl/auchene and zigzag, serve as mechanosensory end organs. These structures are formed by unique combinations of low-threshold mechanoreceptors (LTMRs), Aβ RA-LTMRs, Aδ-LTMRs, and C-LTMRs, and their associated terminal Schwann cells (TSCs). In this study, we investigated the organization, ultrastructure, and maintenance of longitudinal lanceolate complexes at each hair follicle subtype. We found that TSC processes at hair follicles are tiled and that individual TSCs host axonal endings of more than one LTMR subtype. Electron microscopic analyses revealed unique ultrastructural features of lanceolate complexes that are proposed to underlie mechanotransduction. Moreover, Schwann cell ablation leads to loss of LTMR terminals at hair follicles while, in contrast, TSCs remain associated with hair follicles following skin denervation in adult mice and, remarkably, become re-associated with newly formed axons, indicating a TSC-dependence of lanceolate complex maintenance and regeneration in adults.

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