title: Canonical and noncanonical g-protein signaling helps coordinate actin dynamics to promote macrophage phagocytosis of zymosan.
abstract: Both chemotaxis and phagocytosis depend upon actin-driven cell protrusions and cell membrane remodeling. While chemoattractant receptors rely upon canonical G-protein signaling to activate downstream effectors, whether such signaling pathways affect phagocytosis is contentious. Here, we report that Gαi nucleotide exchange and signaling helps macrophages coordinate the recognition, capture, and engulfment of zymosan bioparticles. We show that zymosan exposure recruits F-actin, Gαi proteins, and Elmo1 to phagocytic cups and early phagosomes. Zymosan triggered an increase in intracellular Ca(2+) that was partially sensitive to Gαi nucleotide exchange inhibition and expression of GTP-bound Gαi recruited Elmo1 to the plasma membrane. Reducing GDP-Gαi nucleotide exchange, decreasing Gαi expression, pharmacologically interrupting Gβγ signaling, or reducing Elmo1 expression all impaired phagocytosis, while favoring the duration that Gαi remained GTP bound promoted it. Our studies demonstrate that targeting heterotrimeric G-protein signaling offers opportunities to enhance or retard macrophage engulfment of phagocytic targets such as zymosan.
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ning-Na
authors.initials: NN
authors.lastname: Huang
authors.affiliation: Biological Imaging Facility, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Becker
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Boularan
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Olena
authors.initials: O
authors.lastname: Kamenyeva
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Vural
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Il-Young
authors.initials: IY
authors.lastname: Hwang
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Chong-Shan
authors.initials: CS
authors.lastname: Shi
authors.affiliation: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA jkehrl@niaid.nih.gov.
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D000199:Actins / Q000032:analysis / Q000276:immunology; D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000276:immunology; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000276:immunology; D002460:Cell Line; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010588:Phagosomes / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000276:immunology; D015398:Signal Transduction; D015054:Zymosan / Q000276:immunology*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C510359:ELMO1 protein, mouse; D015054:Zymosan; D051960:GTP-Binding Protein alpha Subunit, Gi2; C498016:Gnai2 protein, mouse; D002118:Calcium