Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor.
Gonorrhea is characterized by a purulent urethral or cervical discharge consisting primarily of neutrophils associated with Neisseria gonorrhoeae. These interactions are facilitated by gonococcal colony opacity-associated (Opa) protein binding to host cellular CEACAM receptors. Of these, CEACAM3 is restricted to neutrophils and contains an immunoreceptor tyrosine-based activation motif (ITAM) reminiscent of that found within certain phagocytic Fc receptors. CEACAM3 was tyrosine phosphorylated by a Src family kinase-dependent process upon infection by gonococci expressing CEACAM-specific Opa proteins. This phosphorylation was necessary for efficient bacterial uptake; however, a less efficient uptake process became evident when kinase inhibitors or mutagenesis of the ITAM were used to prevent phosphorylation. Ligated CEACAM3 was recruited to a cytoskeleton-containing fraction, intense foci of polymerized actin were evident where bacteria attached to HeLa-CEACAM3, and disruption of polymerized actin by cytochalasin D blocked all bacterial uptake by these cells. These data support a model whereby CEACAM3 can mediate the Opa-dependent uptake of N. gonorrhoeae via either an efficient, ITAM phosphorylation-dependent process that resembles phagocytosis or a less efficient, tyrosine phosphorylation-independent mechanism.
McCaw
Shannon E
SE
Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada.
Schneider
Jutta
J
Liao
Edward H
EH
Zimmermann
Wolfgang
W
Gray-Owen
Scott D
SD
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C075729:CEACAM3 protein, human; D002272:Carcinoembryonic Antigen; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C093952:opacity factor receptor, Neisseria gonorrhoeae; C050308:opacity proteins; D019061:src-Family Kinases