title: Pertussis toxin B-pentamer mediates intercellular transfer of membrane proteins and lipids.
abstract: Pertussis toxin (PTx) is the major virulence factor of Bordetella pertussis. The enzymatic or active (A) subunit inactivates host G protein coupled receptor (GPCR) signaling pathways. The non-enzymatic binding (B) subunit also mediates biological effects due to lectin-like binding characteristics, including the induction of T cell receptor (TCR) signaling and subsequent down-regulation of chemokine receptor expression. Here we report another activity attributable to PTxB, facilitating transfer of membrane material between mammalian cells. This activity does not require the TCR, and does not require cell-to-cell contact or cellular aggregation. Rather, membrane vesicles are transferred from donor to recipient cells in a toxin-dependent fashion. Membrane transfer occurs in different cell types, including cultured human T cells, CHO cells, and human primary peripheral blood mononuclear cells. Transfer involves both lipid and integral membrane proteins, as evidenced by the transfer of T and B cell-specific receptor molecules to other PBMCs. Interestingly, membrane transfer activity is a property that PTx shares with some, but not all, cell-aggregating lectins that are mitogenic for human T cells, and appears to be related to the ability to bind certain host cell glycolipids. This phenomenon may represent another mechanism by which pertussis toxin disrupts mammalian intra- and inter-cellular signaling.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Millen
authors.forename: Olivia D
authors.initials: OD
authors.lastname: Schneider
authors.forename: William E
authors.initials: WE
authors.lastname: Miller
authors.forename: John J
authors.initials: JJ
authors.lastname: Monaco
authors.forename: Alison A
authors.initials: AA
authors.lastname: Weiss
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D006801:Humans; D019169:Jurkat Cells; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D043562:Receptors, G-Protein-Coupled; D037342:Pertussis Toxin
references.citation: Biochemistry. 2010 Jul 20;49(28):5954-67
references.pmid: 20515023
references.citation: Eur J Immunol. 2013 Sep;43(9):2430-40
references.pmid: 23749427
references.citation: Sci Signal. 2012 Sep 25;5(243):ra70
references.pmid: 23012657
references.citation: J Immunol. 2005 May 15;174(10):6054-61
references.pmid: 15879099
references.citation: J Cell Biol. 1986 Jul;103(1):171-87
references.pmid: 2424918
references.citation: Proc Natl Acad Sci U S A. 1988 Oct;85(20):7521-5
references.pmid: 2902632
references.citation: Infect Immun. 2004 Jan;72(1):615-20
references.pmid: 14688147
references.citation: J Clin Invest. 2005 Apr;115(4):996-1005
references.pmid: 15841182
references.citation: J Immunol. 1984 Jul;133(1):123-8
references.pmid: 6327821
references.citation: Eur J Biochem. 1980 Feb;104(1):147-53
references.pmid: 6892800
references.citation: Biochemistry. 2012 May 22;51(20):4126-37
references.pmid: 22551306
references.citation: Nat Rev Immunol. 2009 Aug;9(8):581-93
references.pmid: 19498381
references.citation: J Biol Chem. 1992 Dec 25;267(36):25810-5
references.pmid: 1281475
references.citation: Arch Biochem Biophys. 1983 Jul 1;224(1):290-8
references.pmid: 6683482
references.citation: J Exp Med. 1984 Nov 1;160(5):1284-99
references.pmid: 6208306
references.citation: Science. 1989 Oct 27;246(4929):497-500
references.pmid: 2683073
references.citation: Immunology. 2000 Aug;100(4):502-9
references.pmid: 10929078
references.citation: Mol Cell Biol. 2000 Dec;20(24):9149-61
references.pmid: 11094067
references.citation: Cytometry. 1999 Jan 1;35(1):55-63
references.pmid: 10554181
references.citation: Cytometry. 1988 Nov;9(6):619-26
references.pmid: 3061754
references.citation: Eur J Biochem. 1979 Jul;98(1):39-45
references.pmid: 467446
references.citation: Eur J Immunol. 2012 Jul;42(7):1778-84
references.pmid: 22585706
references.citation: Infect Immun. 1999 Jan;67(1):220-9
references.pmid: 9864219
references.citation: Cell Microbiol. 2001 Jan;3(1):45-54
references.pmid: 11207619
references.citation: Infect Immun. 1983 Jun;40(3):1198-203
references.pmid: 6682833
references.citation: Infect Immun. 2007 Aug;75(8):4040-9
references.pmid: 17562776
references.citation: Infect Immun. 1981 Sep;33(3):820-6
references.pmid: 6269999
references.citation: J Exp Med. 1958 Dec 1;108(6):945-56
references.pmid: 13598821
references.citation: Infect Immun. 1991 Dec;59(12):4732-4
references.pmid: 1937835