Unraveling the differential expression of the two isoforms of myelin-associated glycoprotein in a mouse expressing GFP-tagged S-MAG specifically regulated and targeted into the different myelin compartments

Erb, Michael; Flueck, Bettina; Kern, Frances; Erne, Beat; Steck, Andreas; Schaeren-Wiemers, Nicole

doi:10.1016/j.mcn.2005.12.001

Cited by 39 publications

(36 citation statements)

References 46 publications

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“…The amounts of both MAG, another transmembrane protein localized in the paranodal loops (Erb et al, 2006) and CNPase, a cytoplasmic protein implicated in the maintenance of the paranodes (Rasband et al, 2005), were equally reduced by more than 50% in all samples of active and chronic inactive MS lesions (Figs. 3A,B), indicating that these paranodal proteins are stronger affected than NF155 and demonstrating the demyelination in the lesion sites.…”

Section: Comparison Of Nf155-levels In Active and Chronic Inactive Msmentioning

confidence: 99%

Reduced raft‐association of NF155 in active MS‐lesions is accompanied by the disruption of the paranodal junction

Maier

Baron

Hoekstra

2007

Glia

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Neurofascin155 (NF155) is required for the establishment of the paranodal axo-glial junction, the predominant interaction site between myelin and axon. It has been shown that the distribution of NF155 is altered in demyelinating diseases such as multiple sclerosis (MS). However, little is known about the biochemical mechanisms underlying these changes. We therefore compared NF155 in postmortem tissue of active and chronic inactive MS lesions with white matter from healthy controls. Although NF155 showed a very similar expression in all control white matter samples, a strong individual variation was observed in MS-lesions with NF155-levels reduced in most samples. At the same time an NF155-fragment was increased in MS-lesions, suggesting that NF155 is subject to protein degradation in lesion sites. Interestingly, the association of NF155 to membrane microdomains (rafts) was reduced in all lesions, irrespective of the amount of NF155, indicating that membrane association of NF155 was generally affected. Therefore, myelin fractionation experiments were performed to analyze the fate of paranodal proteins during demyelination. Although NF155 was enriched in heavy myelin from both control white matter and active MS-lesions, association of Caspr1/paranodin with heavy myelin was abolished in MS-lesions, demonstrating that paranodal junctions are disrupted. In conclusion, the data support the hypothesis that efficient raft-association of NF155 is essential for the assembly of the paranodal junction and demonstrate that reduced association of NF155 to lipid rafts is accompanied by the disassembly of the paranodal junction and thus contributes to the demyelination process in MS.

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Section: Comparison Of Nf155-levels In Active and Chronic Inactive Msmentioning

confidence: 99%

Reduced raft‐association of NF155 in active MS‐lesions is accompanied by the disruption of the paranodal junction

Maier

Baron

Hoekstra

2007

Glia

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“…MAG is known to be localized mostly in the SL incisures and in the adaxonal domain of myelinating Schwann cells ( Fig. 1 D, double arrow) (Erb et al, 2006). Immunolabeling on teased fibers showed that lgl was present in the abaxonal domain ( We then analyzed the distribution of the epithelial apicojunctional markers par3 and aPKC.…”

Section: Established Epithelial Cell Polarity Proteins Show a Distincmentioning

confidence: 99%

“…S3, available at www.jneurosci.org as supplemental material) [axons are stained for neurofilaments (NF); not pictured for lgl and dlg1]. To confirm that the labeled domain was distinct from the adaxonal domain, we used sciatic nerves of transgenic mice expressing GFP-MAG (Erb et al, 2006). MAG is known to be localized mostly in the SL incisures and in the adaxonal domain of myelinating Schwann cells ( Fig.…”

Section: Established Epithelial Cell Polarity Proteins Show a Distincmentioning

confidence: 99%

Pals1 Is a Major Regulator of the Epithelial-Like Polarization and the Extension of the Myelin Sheath in Peripheral Nerves

Özçelik¹,

Cotter²,

Jacob³

et al. 2010

J. Neurosci.

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Diameter, organization, and length of the myelin sheath are important determinants of the nerve conduction velocity, but the basic molecular mechanisms that control these parameters are only partially understood. Cell polarization is an essential feature of differentiated cells, and relies on a set of evolutionarily conserved cell polarity proteins. We investigated the molecular nature of myelin sheath polarization in connection with the functional role of the cell polarity protein pals1 (Protein Associated with Lin Seven 1) during peripheral nerve myelin sheath extension. We found that, in regard to epithelial polarity, the Schwann cell outer abaxonal domain represents a basolateral-like domain, while the inner adaxonal domain and Schmidt-Lanterman incisures form an apical-like domain. Silencing of pals1 in myelinating Schwann cells in vivo resulted in a severe reduction of myelin sheath thickness and length. Except for some infoldings, the structure of compact myelin was not fundamentally affected, but cells produced less myelin turns. In addition, pals1 is required for the normal polarized localization of the vesicular markers sec8 and syntaxin4, and for the distribution of E-cadherin and myelin proteins PMP22 and MAG at the plasma membrane. Our data show that the polarity protein pals1 plays an essential role in the radial and longitudinal extension of the myelin sheath, likely involving a functional role in membrane protein trafficking. We conclude that regulation of epithelial-like polarization is a critical determinant of myelin sheath structure and function.

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“…Autotypic or autologous gap junctions that join myelin membrane layers in the Schmidt-Lanterman incisures and between adjacent membranes in the paranodal loops are composed mainly of Cx32 [175,176]. The proteins Cx29 and S-MAG colocalise in Schmidt-Lanterman incisures, adaxonal membranes, and paranodal loops [177]. Gap junctions found in the incisures of PNS myelin allow transport of small molecules from the perinuclear cytoplasm to the adaxonal cytoplasm [168].…”

Section: Cellular Junctions As Unique Myelin Microdomainsmentioning

confidence: 99%

White Matter Rafting––Membrane Microdomains in Myelin

DeBruin

Harauz

2006

Neurochem Res

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The myelin membrane comprises a plethora of regions that are compositionally, ultrastructurally, and functionally distinct. Biochemical dissection of oligodendrocytes, Schwann cells, and central and peripheral nervous system myelin by means such as cold-detergent extraction and differential fractionation has led to the identification of a variety of detergent-resistant membrane assemblies, some of which represent putative signalling platforms. We review here the different microdomains that have hitherto been identified in the myelin membrane, particularly lipid rafts, caveolae, and cellular junctions such as the tight junctions that are found in the radial component of the CNS myelin sheath.

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Unraveling the differential expression of the two isoforms of myelin-associated glycoprotein in a mouse expressing GFP-tagged S-MAG specifically regulated and targeted into the different myelin compartments

Cited by 39 publications

References 46 publications

Reduced raft‐association of NF155 in active MS‐lesions is accompanied by the disruption of the paranodal junction

Reduced raft‐association of NF155 in active MS‐lesions is accompanied by the disruption of the paranodal junction

Pals1 Is a Major Regulator of the Epithelial-Like Polarization and the Extension of the Myelin Sheath in Peripheral Nerves

White Matter Rafting––Membrane Microdomains in Myelin

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