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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.

Tiwari-Woodruff SK, Buznikov AG, Vu TQ, Micevych PE, Chen K, Kornblum HI, Bronstein JM - J. Cell Biol. (2001)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.

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.

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In situ hybridization and immunohistochemistry showing OAP-1 expression in mouse forebrain. (A) Dark field photomicrograph of adult rat forebrain after in situ hybridization using 35S–OAP-1 cRNA shows dense neuronal expression of OAP-1 mRNAs in the CA1 region of a P10 mouse hippocampus. The area under the square is shown in B. (B) A high power bright field photomicrograph showing expression of OAP-1 mRNA in oligodendrocytes of the corpus callosum (arrowheads). (C) Using an immunohistochemistry anti–OSP/claudin-11 antibody (Texas red secondary antibody) showed staining primarily in white matter tracts and not in pyramidal cells and astrocytes (large arrow). Small arrows denote the outer borders of corpus callosum. (D) In contrast to OSP/claudin-11, immunohistochemistry using anti–OAP-1 antibody (FITC secondary antibody) in the same section demonstrated widespread staining in white matter tracts and in areas containing pyramidal cells and astrocytes (large arrow).
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Figure 3: In situ hybridization and immunohistochemistry showing OAP-1 expression in mouse forebrain. (A) Dark field photomicrograph of adult rat forebrain after in situ hybridization using 35S–OAP-1 cRNA shows dense neuronal expression of OAP-1 mRNAs in the CA1 region of a P10 mouse hippocampus. The area under the square is shown in B. (B) A high power bright field photomicrograph showing expression of OAP-1 mRNA in oligodendrocytes of the corpus callosum (arrowheads). (C) Using an immunohistochemistry anti–OSP/claudin-11 antibody (Texas red secondary antibody) showed staining primarily in white matter tracts and not in pyramidal cells and astrocytes (large arrow). Small arrows denote the outer borders of corpus callosum. (D) In contrast to OSP/claudin-11, immunohistochemistry using anti–OAP-1 antibody (FITC secondary antibody) in the same section demonstrated widespread staining in white matter tracts and in areas containing pyramidal cells and astrocytes (large arrow).

Mentions: Using in situ hybridization, we found that OAP-1 mRNA was expressed in all areas of the mouse brain with high levels in hippocampal pyramidal neurons and moderate levels in oligodendrocytes of the corpus callosum (Fig. 3A and Fig. B). Unlike OSP/claudin-11 staining in myelin tracts (Fig. 3 C), immunohistochemistry demonstrated that OAP-1 expression was more widespread, consistent with in situ hybridization experiments (Fig. 3 D).


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.

Tiwari-Woodruff SK, Buznikov AG, Vu TQ, Micevych PE, Chen K, Kornblum HI, Bronstein JM - J. Cell Biol. (2001)

In situ hybridization and immunohistochemistry showing OAP-1 expression in mouse forebrain. (A) Dark field photomicrograph of adult rat forebrain after in situ hybridization using 35S–OAP-1 cRNA shows dense neuronal expression of OAP-1 mRNAs in the CA1 region of a P10 mouse hippocampus. The area under the square is shown in B. (B) A high power bright field photomicrograph showing expression of OAP-1 mRNA in oligodendrocytes of the corpus callosum (arrowheads). (C) Using an immunohistochemistry anti–OSP/claudin-11 antibody (Texas red secondary antibody) showed staining primarily in white matter tracts and not in pyramidal cells and astrocytes (large arrow). Small arrows denote the outer borders of corpus callosum. (D) In contrast to OSP/claudin-11, immunohistochemistry using anti–OAP-1 antibody (FITC secondary antibody) in the same section demonstrated widespread staining in white matter tracts and in areas containing pyramidal cells and astrocytes (large arrow).
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Related In: Results  -  Collection

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Figure 3: In situ hybridization and immunohistochemistry showing OAP-1 expression in mouse forebrain. (A) Dark field photomicrograph of adult rat forebrain after in situ hybridization using 35S–OAP-1 cRNA shows dense neuronal expression of OAP-1 mRNAs in the CA1 region of a P10 mouse hippocampus. The area under the square is shown in B. (B) A high power bright field photomicrograph showing expression of OAP-1 mRNA in oligodendrocytes of the corpus callosum (arrowheads). (C) Using an immunohistochemistry anti–OSP/claudin-11 antibody (Texas red secondary antibody) showed staining primarily in white matter tracts and not in pyramidal cells and astrocytes (large arrow). Small arrows denote the outer borders of corpus callosum. (D) In contrast to OSP/claudin-11, immunohistochemistry using anti–OAP-1 antibody (FITC secondary antibody) in the same section demonstrated widespread staining in white matter tracts and in areas containing pyramidal cells and astrocytes (large arrow).
Mentions: Using in situ hybridization, we found that OAP-1 mRNA was expressed in all areas of the mouse brain with high levels in hippocampal pyramidal neurons and moderate levels in oligodendrocytes of the corpus callosum (Fig. 3A and Fig. B). Unlike OSP/claudin-11 staining in myelin tracts (Fig. 3 C), immunohistochemistry demonstrated that OAP-1 expression was more widespread, consistent with in situ hybridization experiments (Fig. 3 D).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.

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.

Show MeSH