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PMID: 11425868 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Restricted accumulation of phosphatidylinositol 3-kinase products in a plasmalemmal subdomain during Fc gamma receptor-mediated phagocytosis.

The Journal of cell biology ·Vol. 153 ·No. 7 ·2001-06-25 ·Pages 1369-80

Marshall JG, Booth JW, Stambolic V, Mak T, Balla T, Schreiber AD, Meyer T, Grinstein S

Abstract

Phagocytosis is a highly localized and rapid event, requiring the generation of spatially and temporally restricted signals. Because phosphatidylinositol 3-kinase (PI3K) plays an important role in the innate immune response, we studied the generation and distribution of 3' phosphoinositides (3'PIs) in macrophages during the course of phagocytosis. The presence of 3'PI was monitored noninvasively in cells transfected with chimeras of green fluorescent protein and the pleckstrin homology domain of either Akt, Btk, or Gab1. Although virtually undetectable in unstimulated cells, 3'PI rapidly accumulated at sites of phagocytosis. This accumulation was sharply restricted to the phagosomal cup, with little 3'PI detectable in the immediately adjacent areas of the plasmalemma. Measurements of fluorescence recovery after photobleaching were made to estimate the mobility of lipids in the cytosolic monolayer of the phagosomal membrane. Stimulation of phagocytic receptors induced a marked reduction of lipid mobility that likely contributes to the restricted distribution of 3'PI at the cup. 3'PI accumulation during phagocytosis was transient, terminating shortly after sealing of the phagosomal vacuole. Two factors contribute to the rapid disappearance of 3'PI: the dissociation of the type I PI3K from the phagosomal membrane and the persistent accumulation of phosphoinositide phosphatases.

MeSH Terms
Adaptor Proteins, Signal Transducing Agammaglobulinaemia Tyrosine Kinase Animals Blood Proteins/genetics Cell Line Cell Membrane Structures/metabolism Macrophages/cytology,metabolism Mice Models, Biological Phagocytosis/physiology Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositol Phosphates/metabolism Phosphatidylinositols/metabolism Phosphoproteins/genetics Phosphoric Monoester Hydrolases/metabolism Protein Binding/physiology Protein Serine-Threonine Kinases Protein Structure, Tertiary/physiology Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-akt Receptors, IgG/metabolism Recombinant Fusion Proteins/genetics,metabolism Sequence Homology, Amino Acid
Chemicals
Adaptor Proteins, Signal Transducing Blood Proteins Gab1 protein, mouse Phosphatidylinositol Phosphates Phosphatidylinositols Phosphoproteins Proto-Oncogene Proteins Receptors, IgG Recombinant Fusion Proteins phosphatidylinositol 3,4,5-triphosphate platelet protein P47 Protein-Tyrosine Kinases Agammaglobulinaemia Tyrosine Kinase Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Phosphoric Monoester Hydrolases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Marshall J G
Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Booth J W
Stambolic V
Mak T
Balla T
Schreiber A D
Meyer T
Grinstein S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.153.7.1369
Published
2001-06-25
Pages
1369-80
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2150726
Subset
IM
Grants
NHLBI NIH HHS · HL28207 · United States
External Links
PubMed source DOI: 10.1083/jcb.153.7.1369 PMC Full Text View journal details
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