Regulation of CD147 cell surface expression: involvement of the proline residue in the CD147 transmembrane domain.
CD147, also known as extracellular matrix metalloproteinase inducer, is a regulator of matrix metalloproteinase production and serves as a signaling receptor for extracellular cyclophilins. Here we demonstrate that the cell surface expression of CD147 is regulated by cyclophilins via the transmembrane domain of CD147. Solution binding experiments demonstrated that the transmembrane domain was both necessary and sufficient for CD147 binding to cyclophilin A (CypA). Treatment with cyclosporin A significantly reduced surface expression of CD147 and of CD8-CD147 fusion protein carrying the extracellular domain of CD8 fused to the transmembrane and cytoplasmic domains of CD147, but did not affect expression of CD8. Peptide binding studies demonstrated specific interaction between CypA and the proline-containing peptide from the CD147 transmembrane domain. Mutation of this proline residue reduced binding of CD147-derived peptides to CypA and also diminished transport of CD147 to the plasma membrane without reducing the total level of CD147 expression. These results suggest involvement of a cyclophilin-related protein in CD147 cell surface expression and provide molecular details for regulation of CD147 trafficking by cyclophilins.
Yurchenko
Vyacheslav
V
Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
Pushkarsky
Tatiana
T
Li
Jian-Hua
JH
Dai
Wei Wei
WW
Sherry
Barbara
B
Bukrinsky
Michael
M
D015703:Antigens, CD / Q000096:biosynthesis*; D051926:Basigin; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D021984:Cyclophilin A / Q000737:chemistry; D016572:Cyclosporine / Q000737:chemistry; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020860:Subtilisin / Q000737:chemistry; D020298:U937 Cells
D015703:Antigens, CD; C497886:BSG protein, human; D010455:Peptides; D011993:Recombinant Fusion Proteins; D051926:Basigin; D049452:Green Fluorescent Proteins; D016572:Cyclosporine; D011392:Proline; D020860:Subtilisin; D021984:Cyclophilin A