Osp/Claudin-11 Forms a Complex with a Novel Member of the Tetraspanin Super Family and β1 Integrin and Regulates Proliferation and Migration of Oligodendrocytes

Tiwari-Woodruff, Seema K.; Buznikov, Alex G.; Vu, Trung Q.; Micevych, Paul E.; Chen, Kendall; Kornblum, Harley I.; Bronstein, Jeff M.

doi:10.1083/jcb.153.2.295

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Article| April 16 2001

Osp/Claudin-11 Forms a Complex with a Novel Member of the Tetraspanin Super Family and β1 Integrin and Regulates Proliferation and Migration of Oligodendrocytes

Seema K. Tiwari-Woodruff,

Seema K. Tiwari-Woodruff

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Alex G. Buznikov,

Alex G. Buznikov

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Trung Q. Vu,

Trung Q. Vu

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Paul E. Micevych,

Paul E. Micevych

bDepartment of Neurobiology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

cDepartment of Molecular and Medical Pharmacology and Pediatrics, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Kendall Chen,

Kendall Chen

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Harley I. Kornblum,

Harley I. Kornblum

cDepartment of Molecular and Medical Pharmacology and Pediatrics, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

dThe Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Jeff M. Bronstein

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

dThe Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

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Author and Article Information

Seema K. Tiwari-Woodruff

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Alex G. Buznikov

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Trung Q. Vu

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Paul E. Micevych

bDepartment of Neurobiology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

cDepartment of Molecular and Medical Pharmacology and Pediatrics, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Kendall Chen

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Harley I. Kornblum

cDepartment of Molecular and Medical Pharmacology and Pediatrics, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

dThe Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Jeff M. Bronstein

aDepartment of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

dThe Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

S.K. Tiwari-Woodruff and A.G. Buznikov contributed equally to this work.

Abbreviations used in this paper: CNS, central nervous system; ECM, extracellular matrix; MBP, myelin basic protein; OAP, OSP-associated protein; ONPG, 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside; OSP; oligodendrocyte-specific protein; PLP, proteolipid protein; SD, synthetic dropout; TJ, tight junction; TM4SF, transmembrane 4 superfamily.

Received: April 24 2000

Revision Requested: February 27 2001

Accepted: February 28 2001

Online ISSN: 1540-8140

Print ISSN: 0021-9525

2001

The Rockefeller University Press

J Cell Biol (2001) 153 (2): 295–306.

https://doi.org/10.1083/jcb.153.2.295

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 β1 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–β1 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 β1 integrin complex in regulating proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair.

2001

The Rockefeller University Press

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Osp/Claudin-11 Forms a Complex with a Novel Member of the Tetraspanin Super Family and β1 Integrin and Regulates Proliferation and Migration of Oligodendrocytes

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