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J. Biol. Chem., Vol. 276, Issue 7, 4853-4862, February 16, 2001
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From the CD81 and CD9, members of the transmembrane-4
superfamily (TM4SF; tetraspanins), form extensive complexes with other
TM4SF proteins, integrins, and other proteins, especially in mild
detergents. In moderately stringent Brij 96 lysis conditions, CD81 and
CD9 complexes are virtually identical to each other, but clearly
distinct from other TM4SF complexes. One of the most prominent proteins within CD81 and CD9 complexes is identified here as FPRP, the 133-kDa
prostaglandin F2
FPRP, a Major, Highly Stoichiometric, Highly Specific CD81-
and CD9-associated Protein*
,¶
Dana-Farber Cancer Institute and the
Department of Pathology, Harvard Medical School, Boston,
Massachusetts 02115 and the § Department of Pathology and
the University of Colorado Cancer Center, University of Colorado
Health Sciences Center, Denver, Colorado 80262
receptor regulatory protein.
FPRP, a cell-surface Ig superfamily protein, associates specifically with CD81 or with CD81 and CD9, but not with integrins or other TM4SF
proteins. In contrast to other CD81- and CD9-associating proteins, FPRP
associates at very high stoichiometry, with essentially 100% of
cell-surface FPRP on 293 cells being CD81- and CD9-associated. Also,
CD81·CD9·FPRP complexes have a discrete size (<4 × 106 Da) as measured by gel permeation chromatography
and remain intact after disruption of cholesterol-rich membrane
microdomains by methyl-
-cyclodextrin. Although CD81 associated with
both 
3 integrin and FPRP in 293 cells, the
31·CD81 and CD81·CD9·FPRP
complexes were distinct, as determined by immunoprecipitation and
immunodepletion experiments. In conclusion, our data affirm the
existence of distinct TM4SF complexes with unique compositions and
specifically characterize FPRP as the most robust, highly
stoichiometric CD81- and/or CD9-associated protein yet described.
*
This work was supported by National Institutes of Health
Grant GM38903 (to M. E. H.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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