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ABSTRACT: 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.
The Journal of Cell Biology 05/2001; 153(2):295-305. · 10.26 Impact Factor
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ABSTRACT: Oligodendrocyte-specific protein (OSP/claudin-11) is a major component of CNS myelin and has been recently added to the claudin family of tight junction proteins. In this study, the developmental expression of OSP/claudin-11 was determined using in situ hybridization, immunohistochemistry (IH), and Western blot analysis. OSP/claudin-11 mRNA was expressed in a bimodal fashion. During prenatal development, OSP/claudin-11 mRNA was abundant in developing meninges, in areas adjacent to cartilage, and in mesoderm. In postnatal animals, OSP/claudin-11 was expressed primarily in developing oligodendrocytes and to a lesser extent, in testes. Double-labeled IH using O2-A progenitor cells revealed that OSP/claudin-11 expression occurs from the early progenitor stage and continues in mature oligodendrocytes. Electron microscopic IH localized OSP/claudin-11 to laminar myelin in the adult CNS. Western blot analysis of OSP/claudin-11 in developing brain revealed the expression of two separate transcripts that were developmentally regulated. These data demonstrate that OSP/claudin-11 expression is highly regulated during development and, therefore, may play an important role in growth and differentiation of oligodendrocytes and other cells outside the CNS.
Journal of Neuroscience Research 06/2000; 60(3):284-90. · 2.74 Impact Factor
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ABSTRACT: Oligodendrocyte-specific protein (OSP) is a recently isolated and cloned, 207-aa, hydrophobic, four-transmembrane protein found in CNS myelin. It represents approximately 7% of total myelin protein. The OSP cDNA sequence has no significant homology with previously reported genes, but the predicted protein structure suggests that OSP is a CNS homologue of peripheral myelin protein-22. We previously reported the presence of anti-OSP Abs in the cerebrospinal fluid of relapsing-remitting multiple sclerosis (MS) patients, but not control patient groups. In this study, we tested the ability of a panel of 20-mer peptides with 10-aa overlaps, representing the sequence of murine OSP, to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. SJL mice challenged with murine OSP peptides 52-71, 82-101, 102-121, 142-161, 182-201, and 192-207 exhibited clinical EAE. OSP:52-71 elicited severe relapsing-remitting EAE in some individuals. All other encephalitogenic peptides elicited, at most, a loss of tail tonicity from which the mice most often completely recovered. Mononuclear cell infiltrates and focal demyelination characteristic of EAE were evident. T cell proliferative responses were seen with all encephalitogenic peptides except 142-161 and 182-201. OSP peptides 72-91 and 132-151 did not cause clinical EAE, but did elicit robust proliferative responses. B10.PL and PL/J mice challenged with the same OSP peptide doses as SJL mice did not exhibit clinical EAE. These results in the SJL EAE model, together with the results from MS patient clinical samples, make OSP a promising candidate for autoantigenic involvement in MS.
The Journal of Immunology 07/1999; 162(12):7501-9. · 5.79 Impact Factor
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ABSTRACT: An oligodendrocyte-specific protein (OSP) cDNA was recently identified and found to be expressed primarily in oligodendrocytes and has a deduced amino acid sequence similar to that of peripheral myelin protein 22 (PMP-22). We raised antibodies against a synthetic peptide corresponding to OSP amino acid residues 179-194 which reacted with a 22 kd protein in mouse CNS. OSP immunoreactivity localized to spinal cord white matter tracts using immunohistochemistry in a similar distribution to that of MBP. OSP localized to CNS myelin biochemically with more than a 30-fold enrichment measured in purified myelin. We further purified the proteolipid fraction of myelin and determined that OSP contributes approximately 7% of total myelin protein making it the third most abundant protein in CNS myelin. No binding was found to several agglutinins or a HNK1-specific antibody suggesting that OSP is not a glycoprotein.
Journal of Neuroscience Research 01/1998; 50(5):713-20. · 2.74 Impact Factor
