OSP/claudin-11 forms a complex with a novel member of the tetraspanin super family and beta1 integrin and regulates proliferation and migration of oligodendrocytes.
Oligodendrocyte-specific protein (OSP)/claudin-11 is a major component of central nervous system myelin and forms tight junctions (TJs) within myelin sheaths. TJs are essential for forming a paracellular barrier and have been implicated in the regulation of growth and differentiation via signal transduction pathways. We have identified an OSP/claudin-11-associated protein (OAP)1, using a yeast two-hybrid screen. OAP-1 is a novel member of the tetraspanin superfamily, and it is widely expressed in several cell types, including oligodendrocytes. OAP-1, OSP/claudin-11, and beta1 integrin form a complex as indicated by coimmunoprecipitation and confocal immunocytochemistry. Overexpression of OSP/claudin-11 or OAP-1 induced proliferation in an oligodendrocyte cell line. Anti-OAP-1, anti-OSP/claudin-11, and anti-beta1 integrin antibodies inhibited migration of primary oligodendrocytes, and migration was impaired in OSP/claudin-11-deficient primary oligodendrocytes. These data suggest a role for OSP/claudin-11, OAP-1, and beta1 integrin complex in regulating proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair.
Tiwari-Woodruff
S K
SK
Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.
Buznikov
A G
AG
Vu
T Q
TQ
Micevych
P E
PE
Chen
K
K
Kornblum
H I
HI
Bronstein
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D057167:Claudins; D005353:Fibronectins / Q000378:metabolism; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000737:chemistry / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D016415:Sequence Alignment; D059470:Tetraspanins; D019108:Tight Junctions / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D000906:Antibodies; D057167:Claudins; C492354:Cldn11 protein, mouse; D005353:Fibronectins; D019012:Integrin beta1; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D059470:Tetraspanins; C426223:Tspan3 protein, mouse