title: Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties.
abstract: 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.
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Denninger
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Andrew
authors.initials: A
authors.lastname: Breglio
authors.affiliation: Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Maheras
authors.affiliation: European Synchrotron Radiation Facility, Grenoble, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: LeDuc
authors.affiliation: Institut Laue-Langevin, Grenoble, France.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cristiglio
authors.affiliation: Institut Laue-Langevin, Grenoble, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Demé
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan; Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan; Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gow
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts. Electronic address: kirschnd@bc.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Kirschner
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000378:metabolism; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D004058:Diffusion; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism*; D033363:Neutron Diffraction; D009900:Optic Nerve / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D014867:Water / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D057167:Claudins; C492354:Cldn11 protein, mouse; D014867:Water