Coordinated internodal and paranodal adhesion controls accurate myelination by oligodendrocytes

Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enr...

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Vydané v:The Journal of cell biology Ročník 218; číslo 9; s. 2887
Hlavní autori: Elazar, Nimrod, Vainshtein, Anya, Rechav, Katya, Tsoory, Michael, Eshed-Eisenbach, Yael, Peles, Elior
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 02.09.2019
Predmet:
Animals
Axons - metabolism
Cell Adhesion - genetics
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules, Neuronal - genetics
Cell Adhesion Molecules, Neuronal - metabolism
Intercellular Junctions - genetics
Intercellular Junctions - metabolism
Mice
Mice, Knockout
Myelin Sheath - genetics
Myelin Sheath - metabolism
Myelin-Associated Glycoprotein - genetics
Myelin-Associated Glycoprotein - metabolism
Oligodendroglia - cytology
Oligodendroglia - metabolism
ISSN:1540-8140, 1540-8140
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Popis
Shrnutí:Oligodendrocyte-axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enriched at the internodes below the compact myelin, whereas NF155, which binds the axonal Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and the terminal loops of the myelin sheath. Here we report that Cadm4-, MAG-, and Caspr-mediated adhesion cooperate during myelin membrane ensheathment. Genetic deletion of either Cadm4 and MAG or Cadm4 and Caspr resulted in the formation of multimyelinated axons due to overgrowth of the myelin away from the axon and the forming paranodal junction. Consequently, these mice displayed paranodal loops either above or underneath compact myelin. Our results demonstrate that accurate placement of the myelin sheath by oligodendrocytes requires the coordinated action of internodal and paranodal CAMs.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1540-8140
1540-8140
DOI:10.1083/jcb.201906099