期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 43, 页码 11003-11014出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3285-08.2008
关键词
myelin; axoglial junction; paranode; septate-like junctions; Caspr; neurofascin
资金
- Multiple Sclerosis Society of Canada
- Canadian Institutes of Health Research
- Montreal Neurological Institute
- Killam Foundation
- Fonds de la Recherche en Sante du Quebec
Paranodal axoglial junctions are essential for the segregation of myelinated axons into distinct domains and efficient conduction of action potentials. Here, we show that netrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNS myelin. We then address whether netrin-1 signaling influences paranodal adhesion between oligodendrocytes and axons. In the absence of netrin-1 or DCC function, oligodendroglial paranodes initially develop and mature normally but later become disorganized. Lack of DCC or netrin-1 resulted in detachment of paranodal loops from the axonal surface and the disappearance of transverse bands. Furthermore, the domain organization of myelin is compromised in the absence of netrin-1 signaling: K+ channels inappropriately invade the paranodal region, and the normally restricted paranodal distribution of Caspr expands longitudinally along the axon. Our findings identify an essential role for netrin-1 and DCC regulating the maintenance of axoglial junctions.
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