Uptake and intracellular transportation of a bacterial surface protein in lymphoid cells.
Some strains of the human pathogen Streptococcus pyogenes express a surface protein called protein H, which is released from the streptococcal surface by a cysteine proteinase produced by the bacteria. Here, we find that soluble protein H binds to the surface of lymphocytes and granulocytes, and that the molecule is taken up by lymphocytes and transported to the perinuclear region. The translocation over the cell membrane is rapid, and the uptake and intracellular transportation is not dependent on actin polymerization. Protein H could be immunoprecipitated from cell extracts and nuclear preparations of lymphocytes, and analysis of molecular interactions between protein H and proteins of different cellular compartments demonstrated a binding to nucleophosmin/ B23, a protein known to shuttle between the cytoplasm and the nucleus, and to the nuclear proteins SET and hnRNP A2/B1. Nucleophosmin/B23 was co-immunoprecipitated with protein H from cell and nuclear extracts, and binding experiments, including kinetic analyses, suggest that protein H dissociating from nucleophosmin/B23 complexes in the perinuclear region or in the nucleus binds to proteins SET and hnRNP A2/B1. Finally, the uptake and intracellular transportation of protein H was found to result in a cytostatic effect on B and T lymphocytes.
Frick
Inga-Maria
IM
Department of Cell and Molecular Biology, Lund University, BMC, B14, Tornavägen 10, S-221 84 Lund, Sweden. Ina-Maria.Frick@medkem.lu.se
Axcrona
Karol
K
Härdig
Ylva
Y
Tapper
Hans
H
Gustafsson
Lotta
L
Kellner
Roland
R
Leanderson
Tomas
T
Björck
Lars
L
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D013297:Streptococcus pyogenes / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity
D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D010446:Peptide Fragments; C064006:protein H, Streptococcus; D000090243:Nucleophosmin