title: Normal autophagic activity in macrophages from mice lacking Gαi3, AGS3, or RGS19.
abstract: In macrophages autophagy assists antigen presentation, affects cytokine release, and promotes intracellular pathogen elimination. In some cells autophagy is modulated by a signaling pathway that employs Gαi3, Activator of G-protein Signaling-3 (AGS3/GPSM1), and Regulator of G-protein Signaling 19 (RGS19). As macrophages express each of these proteins, we tested their importance in regulating macrophage autophagy. We assessed LC3 processing and the formation of LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3(-/-), Gpsm1(-/-), or Rgs19(-/-) mice following amino acid starvation or Nigericin treatment. In addition, we evaluated rapamycin-induced autophagic proteolysis rates by long-lived protein degradation assays and anti-autophagic action after rapamycin induction in wild type, Gnai3(-/-), and Gpsm1(-/-) macrophages. In similar assays we compared macrophages treated or not with pertussis toxin, an inhibitor of GPCR (G-protein couple receptor) triggered Gαi nucleotide exchange. Despite previous findings, the level of basal autophagy, autophagic induction, autophagic flux, autophagic degradation and the anti-autophagic action in macrophages that lacked Gαi3, AGS3, or RGS19; or had been treated with pertussis toxin, were similar to controls. These results indicate that while Gαi signaling may impact autophagy in some cell types it does not in macrophages.
authors: B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Ali
authors: A
authors: Vural
authors: Travis J
authors: TJ
authors: McQuiston
authors: Joe B
authors: JB
authors: Blumer
authors: Chung
authors: C
authors: Park
authors: Il-Young
authors: IY
authors: Hwang
authors: Yolanda
authors: Y
authors: Williams-Bey
authors: Chong-Shan
authors: CS
authors: Shi
authors: Dzwokai Zach
authors: DZ
authors: Ma
authors: John H
authors: JH
authors: Kehrl
mesh_terms: D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000502:physiology*; D020730:Guanine Nucleotide Dissociation Inhibitors; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D059748:Proteolysis; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C498915:Gpsm1 protein, mouse; D020730:Guanine Nucleotide Dissociation Inhibitors; D020710:RGS Proteins; C097187:regulator of G-protein signalling 19; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C417708:Gnai3 protein, mouse