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Published online 16 April 2001. doi:10.1083/jcb.153.2.295
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© The Rockefeller University Press, 0021-9525/2001//295 $5.00
The Journal of Cell Biology, Volume 153, Number 2, , 2001 295-306

Original Article

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-Woodruffa, Alex G. Buznikova, Trung Q. Vua, Paul E. Micevychb,c, Kendall Chena, Harley I. Kornblumc,d, and Jeff M. Bronsteina,d

a Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095
b Department of Neurobiology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095
c Department of Molecular and Medical Pharmacology and Pediatrics, University of California at Los Angeles School of Medicine, Los Angeles, California 90095
d The Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095
UCLA School of Medicine, Dept. of Neurology, RNRC 710 Westwood Plaza, Los Angeles, CA 90024.(310) 206-9819(310) 794-2158

jbronste{at}ucla.edu

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.

Key Words: tight junctions • myelin • TM4SF • brain • OAP-1

© 2001 The Rockefeller University Press

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.


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