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Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2.

In neutrophils, superoxide anion production generally accompanies chemotaxis and functions in killing invading pathogens. The GIT2 GTPase-activating protein binds to the guanine nucleotide-exchange factor alphaPIX. Here we show that GIT2 was necessary for directional chemotaxis and for the suppression of superoxide production in G protein-coupled receptor-stimulated neutrophils. GIT2 was also necessary for the orientation of superoxide production toward chemoattractant sources. GIT2 suppressed the activity of ADP ribosylation factor 1 and was a component of the Gbetagamma subunit-mediated direction-sensing machinery 'downstream' of G protein-coupled receptor signaling. This study establishes a function for GIT2 in linking chemotaxis and superoxide production in neutrophils and shows that loss of GIT2 in vivo leads to an immunodeficient state.

Pubmed ID: 16715100


  • Mazaki Y
  • Hashimoto S
  • Tsujimura T
  • Morishige M
  • Hashimoto A
  • Aritake K
  • Yamada A
  • Nam JM
  • Kiyonari H
  • Nakao K
  • Sabe H


Nature immunology

Publication Data

July 20, 2006

Associated Grants


Mesh Terms

  • ADP-Ribosylation Factor 1
  • Actins
  • Animals
  • Aspergillosis
  • Cell Cycle Proteins
  • Chemotactic Factors
  • Chemotaxis
  • Complement C5a
  • Disease Susceptibility
  • Enzyme Activation
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Guanine Nucleotide Exchange Factors
  • Immunologic Deficiency Syndromes
  • Interleukin-8
  • Lung
  • Lung Diseases, Fungal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiprotein Complexes
  • N-Formylmethionine Leucyl-Phenylalanine
  • Neutrophils
  • Phosphatidylinositol Phosphates
  • Phosphoproteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • Superoxides
  • p21-Activated Kinases
  • rac1 GTP-Binding Protein