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The raft-associated protein MAL is required for maintenance of proper axon--glia interactions in the central nervous system.

Schaeren-Wiemers N, Bonnet A, Erb M, Erne B, Bartsch U, Kern F, Mantei N, Sherman D, Suter U - J. Cell Biol. (2004)

Bottom Line: These structural changes were accompanied by a marked reduction of contactin-associated protein/paranodin, neurofascin 155 (NF155), and the potassium channel Kv1.2, whereas nodal clusters of sodium channels were unaltered.Biochemical analysis revealed reduced myelin-associated glycoprotein, myelin basic protein, and NF155 protein levels in myelin and myelin-derived rafts.Our results demonstrate a critical role for MAL in the maintenance of central nervous system paranodes, likely by controlling the trafficking and/or sorting of NF155 and other membrane components in oligodendrocytes.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology, Department of Research, University Hospital Basel, 4056 Basel, Switzerland. Nicole.Schaeren-Wiemers@unibas.ch

ABSTRACT
The myelin and lymphocyte protein (MAL) is a tetraspan raft-associated proteolipid predominantly expressed by oligodendrocytes and Schwann cells. We show that genetic ablation of mal resulted in cytoplasmic inclusions within compact myelin, paranodal loops that are everted away from the axon, and disorganized transverse bands at the paranode--axon interface in the adult central nervous system. These structural changes were accompanied by a marked reduction of contactin-associated protein/paranodin, neurofascin 155 (NF155), and the potassium channel Kv1.2, whereas nodal clusters of sodium channels were unaltered. Initial formation of paranodal regions appeared normal, but abnormalities became detectable when MAL started to be expressed. Biochemical analysis revealed reduced myelin-associated glycoprotein, myelin basic protein, and NF155 protein levels in myelin and myelin-derived rafts. Our results demonstrate a critical role for MAL in the maintenance of central nervous system paranodes, likely by controlling the trafficking and/or sorting of NF155 and other membrane components in oligodendrocytes.

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Normal peripheral nerves in mal-deficient mice. Morphology of sciatic nerves from 2.5-mo-old KO mice. EM analysis of cross-sectioned sciatic nerve tissues shows normal myelinated (A) and unmyelinated (B) axons of mal KO mice. (C) Longitudinal section of a sciatic nerve shows normal paranodal morphology in KO. Asterisk indicates an axon. SC indicates a Schwann cell body. Bars: A, 50 μm; B, 1 μm; C, 0.5 μm.
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fig2: Normal peripheral nerves in mal-deficient mice. Morphology of sciatic nerves from 2.5-mo-old KO mice. EM analysis of cross-sectioned sciatic nerve tissues shows normal myelinated (A) and unmyelinated (B) axons of mal KO mice. (C) Longitudinal section of a sciatic nerve shows normal paranodal morphology in KO. Asterisk indicates an axon. SC indicates a Schwann cell body. Bars: A, 50 μm; B, 1 μm; C, 0.5 μm.

Mentions: MAL is highly expressed by Schwann cells in developing and adult peripheral nerves (Fig. 1 B). Furthermore, mice overexpressing MAL showed progressive segregation of unmyelinated PNS axons (Frank et al., 2000). Thus, we examined the sciatic nerves of 2-mo-old KO mice (Fig. 2). No significant alterations of myelinated fibers (Fig. 2 A) and nonmyelinating Schwann cells engulfing small caliber axons (Fig. 2 B, asterisk) were found. In addition, we used teased sciatic nerve fiber preparations to assess the integrity of nodes of Ranvier by immunostaining with the paranodal marker E-cadherin, contactin-associated protein/paranodin (Caspr), and the juxtaparanodal marker Kv1.1. No major changes were detected in the KO mice (unpublished data). Ultrastructural analysis of nodal and paranodal regions of PNS fibers revealed a normal morphology (Fig. 2 C). We conclude that MAL is not essential for the formation of peripheral nerves.


The raft-associated protein MAL is required for maintenance of proper axon--glia interactions in the central nervous system.

Schaeren-Wiemers N, Bonnet A, Erb M, Erne B, Bartsch U, Kern F, Mantei N, Sherman D, Suter U - J. Cell Biol. (2004)

Normal peripheral nerves in mal-deficient mice. Morphology of sciatic nerves from 2.5-mo-old KO mice. EM analysis of cross-sectioned sciatic nerve tissues shows normal myelinated (A) and unmyelinated (B) axons of mal KO mice. (C) Longitudinal section of a sciatic nerve shows normal paranodal morphology in KO. Asterisk indicates an axon. SC indicates a Schwann cell body. Bars: A, 50 μm; B, 1 μm; C, 0.5 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172435&req=5

fig2: Normal peripheral nerves in mal-deficient mice. Morphology of sciatic nerves from 2.5-mo-old KO mice. EM analysis of cross-sectioned sciatic nerve tissues shows normal myelinated (A) and unmyelinated (B) axons of mal KO mice. (C) Longitudinal section of a sciatic nerve shows normal paranodal morphology in KO. Asterisk indicates an axon. SC indicates a Schwann cell body. Bars: A, 50 μm; B, 1 μm; C, 0.5 μm.
Mentions: MAL is highly expressed by Schwann cells in developing and adult peripheral nerves (Fig. 1 B). Furthermore, mice overexpressing MAL showed progressive segregation of unmyelinated PNS axons (Frank et al., 2000). Thus, we examined the sciatic nerves of 2-mo-old KO mice (Fig. 2). No significant alterations of myelinated fibers (Fig. 2 A) and nonmyelinating Schwann cells engulfing small caliber axons (Fig. 2 B, asterisk) were found. In addition, we used teased sciatic nerve fiber preparations to assess the integrity of nodes of Ranvier by immunostaining with the paranodal marker E-cadherin, contactin-associated protein/paranodin (Caspr), and the juxtaparanodal marker Kv1.1. No major changes were detected in the KO mice (unpublished data). Ultrastructural analysis of nodal and paranodal regions of PNS fibers revealed a normal morphology (Fig. 2 C). We conclude that MAL is not essential for the formation of peripheral nerves.

Bottom Line: These structural changes were accompanied by a marked reduction of contactin-associated protein/paranodin, neurofascin 155 (NF155), and the potassium channel Kv1.2, whereas nodal clusters of sodium channels were unaltered.Biochemical analysis revealed reduced myelin-associated glycoprotein, myelin basic protein, and NF155 protein levels in myelin and myelin-derived rafts.Our results demonstrate a critical role for MAL in the maintenance of central nervous system paranodes, likely by controlling the trafficking and/or sorting of NF155 and other membrane components in oligodendrocytes.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology, Department of Research, University Hospital Basel, 4056 Basel, Switzerland. Nicole.Schaeren-Wiemers@unibas.ch

ABSTRACT
The myelin and lymphocyte protein (MAL) is a tetraspan raft-associated proteolipid predominantly expressed by oligodendrocytes and Schwann cells. We show that genetic ablation of mal resulted in cytoplasmic inclusions within compact myelin, paranodal loops that are everted away from the axon, and disorganized transverse bands at the paranode--axon interface in the adult central nervous system. These structural changes were accompanied by a marked reduction of contactin-associated protein/paranodin, neurofascin 155 (NF155), and the potassium channel Kv1.2, whereas nodal clusters of sodium channels were unaltered. Initial formation of paranodal regions appeared normal, but abnormalities became detectable when MAL started to be expressed. Biochemical analysis revealed reduced myelin-associated glycoprotein, myelin basic protein, and NF155 protein levels in myelin and myelin-derived rafts. Our results demonstrate a critical role for MAL in the maintenance of central nervous system paranodes, likely by controlling the trafficking and/or sorting of NF155 and other membrane components in oligodendrocytes.

Show MeSH
Related in: MedlinePlus