Journal
BIOPHYSICAL JOURNAL
Volume 109, Issue 7, Pages 1387-1397Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2015.08.012
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Funding
- Fondation pour l'Aide a la Recherche sur la Sclerose en Plaques (ARSEP Foundation)
- L'Association Europeenne contre les Leucodystrophies - ELA (ELA Foundation) [ELA2008-009C4, ELA2010-042C5]
- Boston College Institutional Research Funds
- Burroughs Wellcome Fund (Collaborative Research Travel Grant)
- National Institutes of Health, NIDCD [DC006262]
- National Multiple Sclerosis Society [RG4639]
- Carls Foundation of Michigan
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The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function.
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