The raft-associated protein MAL is required for maintenance of proper axon--glia interactions in the central nervous system.
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.
Schaeren-Wiemers
Nicole
N
Neurobiology, Department of Research, University Hospital Basel, 4056 Basel, Switzerland. Nicole.Schaeren-Wiemers@unibas.ch
Bonnet
Annick
A
Erb
Michael
M
Erne
Beat
B
Bartsch
Udo
U
Kern
Frances
F
Mantei
Ned
N
Sherman
Diane
D
Suter
Ueli
U
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D051663:Kv1.2 Potassium Channel; D021962:Membrane Microdomains / Q000378:metabolism* / Q000648:ultrastructure; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D021381:Protein Transport / Q000235:genetics; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D011901:Ranvier's Nodes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D015815:Cell Adhesion Molecules; C496970:Kcna2 protein, mouse; D051663:Kv1.2 Potassium Channel; C569027:Mal protein, mouse; D026901:Membrane Transport Proteins; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D018992:Myelin-Associated Glycoprotein; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011510:Proteolipids