beta-Arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae.
Pneumococci traverse eukaryotic cells within vacuoles without intracytoplasmic multiplication. The platelet-activating factor receptor (PAFr) has been suggested as a portal of entry. Pneumococci colocalized with PAFr on endothelial cells and PAFr-/- mice showed a substantially impaired ability to support bacterial translocation, particularly from blood to brain. Pneumococci-induced colocalization of PAFr and beta-arrestin 1 at the plasma membrane of endothelial cells and PAFr-mediated pneumococcal uptake in transfected COS cells were greatly increased by cotransfection with the scaffold/adapter protein beta-arrestin 1. Activation of extracellular signal-regulated kinase kinases was required for uptake and was limited to the cytoplasmic compartment, consistent with activation by beta-arrestin rather than PAFr. Uptake of the pneumococcal vacuole involved clathrin, and half the bacteria proceeded into vacuoles marked by Rab5 and later Rab7, the classical route to the lysosome. Overexpression of beta-arrestin in endothelial cells decreased colocalization with Rab7. We conclude that the association of beta-arrestin with the PAFr contributes to successful translocation of pneumococci.
Radin
Jana N
JN
Department of Infectious Diseases, St. Jude Children's Research Hospital, Mailstop 320 IRC 8057, 332 N. Lauderdale Rd., Memphis, TN 38105, USA.
Orihuela
Carlos J
CJ
Murti
Gopal
G
Guglielmo
Christopher
C
Murray
Peter J
PJ
Tuomanen
Elaine I
EI
D000818:Animals; D019390:Arrestins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000737:chemistry; D004705:Endocytosis; D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D020691:rab GTP-Binding Proteins / Q000378:metabolism
C000605255:Arrb1 protein, mouse; D019390:Arrestins; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; C039351:platelet activating factor receptor; D020928:Mitogen-Activated Protein Kinases; D020691:rab GTP-Binding Proteins