β-Arrestin 1 Participates in Platelet-Activating Factor Receptor-Mediated Endocytosis of Streptococcus pneumoniae

Abstract

Pneumococci traverse eukaryotic cells within vacuoles without intracytoplasmic multiplication. The plateletactivating 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 ␤-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 ␤-arrestin 1. Activation of extracellular signal-regulated kinase kinases was required for uptake and was limited to the cytoplasmic compartment, consistent with activation by ␤-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 ␤-arrestin in endothelial cells decreased colocalization with Rab7. We conclude that the association of ␤-arrestin with the PAFr contributes to successful translocation of pneumococci.

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

“…The small number of pneumococcus-containing vacuoles that underwent recycling to the apical surface demonstrated colocalization with Ras-related protein 11, which regulates endosome recycling. These findings suggest that the pneumococcus-induced interactions between PAF receptor and ␤-arrestin contribute to the transcellular penetration of HBMECs by S. pneumoniae (197). Group B streptococcus.…”

“…S. pneumoniae induces the translocation of ␤-arrestin from the cytosol to the plasma membrane, where it colocalizes with the PAF receptor. This interaction also stimulates mitogen-activated protein kinase signaling, which is required for pneumococcal uptake (197). Vacuoles containing S. pneumoniae colocalized with early and late endosomal markers; however, increased expression of ␤-arrestin subverted these vacuoles from lysosomal trafficking and promoted the transcytosis of viable bacteria.…”

“…In contrast, transparent pneumococci may undergo some recycling back to the apical surface; however, by 5 h postinfection in a Transwell system, the majority of bacteria had translocated to the basolateral chamber (193). The invasion of HBMECs by transparent S. pneumoniae depends on phosphorylcholine, the PAF receptor, and ␤-arrestin, which targets G-protein-coupled receptors (such as PAF receptor) to clathrin-coated vesicles (193,197). S. pneumoniae induces the translocation of ␤-arrestin from the cytosol to the plasma membrane, where it colocalizes with the PAF receptor.…”

The role of CCR5 in vaccinia virus pathogenesis

“…Furthermore, the receptor-ß-arrestin complex is sequestered in clathrin-coated pits, which then become clathrin-coated vesicles via interaction with dynamin (728). Rab5-and rab7-dependent vesicle fusion processes are involved in trafficking of the vesicles from early to late endosomes to lysosomes (352,534,713,717). Once internalized, receptors accumulate in peri-nuclear recycling endosomes and are recycled back to the cell surface in their dephosphorylated form (459).…”

Impact of the glpQ2 Gene on Virulence in a Streptococcus pneumoniae Serotype 19A Sequence Type 320 Strain

“…The structure of ChoP resembles that of the platelet-activating factor (PAF), and thus, ChoP on S. pneumoniae can interact directly with the host PAF receptor (7) and allow S. pneumoniae to transit the epithelial and endothelial layers during invasion (8). The conjugation between ChoP and the PAF receptor is important for pneumococcal sequestration during immune clearance and systemic dissemination, since mice deficient in PAF receptor or treated with PAF receptor antagonist abolish pneumococcal pneumonia progression to cause sepsis and meningitis (9).…”