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Tetraspanin protein CD 9 interacts with metalloprotease CD 10 and enhances its release via exosomes
Author(s) -
Mazurov Dmitriy,
Barbashova Lubov,
Filatov Alexander
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12110
Subject(s) - tetraspanin , microvesicles , microbiology and biotechnology , chemistry , cd81 , metalloproteinase , exosome , transmembrane protein , intracellular , extracellular , transmembrane domain , cell , biology , biochemistry , receptor , matrix metalloproteinase , microrna , gene , hepatitis c virus , virus , virology
Tetraspanins interact with a wide variety of transmembrane and intracellular proteins called molecular partners, and modulate their function. In this article, we describe a new partner of tetraspanin web, membrane metalloprotease CD 10, which is selectively associated with CD 9. By constructing chimeras between tetraspanins CD 9 and CD 82 (the latter does not interact with CD 10) or by using site‐directed mutagenesis, we determined that a portion of the large extracellular loop from the CCG motif to transmembrane domain 4, as well as the C ‐terminal tail of CD 9, are involved in the interaction with CD 10. The stable expression of wild‐type CD 9 in K 562 CD 10‐positive cells enhanced the level of CD 10 released with exosomes five‐fold. In contrast, the expression of chimeric CD 9, which contained the cytoplasmic C ‐terminal domain from CD 82, had little effect on CD 10 release. Short hairpin RNA knockdown of CD 9 expression in Nalm‐6 pre‐B cells resulted in a two‐fold reduction in the amount of endogenous CD 10 released with microvesicles. The peptidase activity of CD 10 measured either on cells or on exosomes correlated with the level of CD 10 expression, and was not significantly modulated by CD 9 expression as such. Our data suggest that the interaction of CD 10 with tetraspanin CD 9 can play an important role in the redistribution of peptidase activity from the cell surface to outer microenvironments. In bone marrow, where CD 10 presumably contributes to the maturation of pre‐ B cells and migration of B cells to the blood circulation, release of CD 10 peptidase activity with exosomes may effectively regulate extracellular matrix microenvironments. Structured digital abstractCD9 physically interacts with CD179b , Tetraspanin-9 , CD63 , CD81 , HLA class II , Uncharacterized protein C14orf166B , Tetraspanin-14 , HLA class I , Galactokinase , Protein disulfide-isomerase A6 , CD98 , CD19 , CD316 , CD146 , CD92 , Annexin A6 , CD156c , CD71 , CD10 , CD29 , CD315 , DAAM1 and CD49f by anti bait coimmunoprecipitation ( View interaction ) CD10 physically interacts with CD9 by anti bait coimmunoprecipitation (View Interaction: 1 , 2 , 3 , 4 ) CD10 physically interacts with CD179b , Protein FAM207A , CD9 , CD81 , Uncharacterized protein C22orf13 , HLA class II , Uncharacterized protein C3orf26 , HLA class I , Protein C14orf21 , Annexin A6 and DAAM1 by anti bait coimmunoprecipitation ( View interaction )