GBF1 bears a novel phosphatidylinositol-phosphate binding module, BP3K, to link PI3Kγ activity with Arf1 activation involved in GPCR-mediated neutrophil chemotaxis and superoxide production.

Molecular Biology of the Cell
Yuichi MazakiHisataka Sabe

Abstract

Most chemoattractants for neutrophils bind to the Gα(i) family of heterotrimeric G protein-coupled receptors (GPCRs) and release Gβγ subunits to activate chemotaxis and superoxide production. GIT2, a GTPase-activating protein for Arf1, forms a complex with Gβγ and is integral for directional sensing and suppression of superoxide production. Here we show that GBF1, a guanine nucleotide exchanging factor for Arf-GTPases, is primarily responsible for Arf1 activation upon GPCR stimulation and is important for neutrophil chemotaxis and superoxide production. We find that GBF1 bears a novel module, namely binding to products of phosphatidyl inositol 3-kinase (PI3K), which binds to products of PI3Kγ. Through this binding, GBF1 is translocated from the Golgi to the leading edge upon GPCR stimulation to activate Arf1 and recruit p22phox and GIT2 to the leading edge. Moreover, GBF1-mediated Arf1 activation is necessary to unify cell polarity during chemotaxis. Our results identify a novel mechanism that links PI3Kγ activity with chemotaxis and superoxide production in GPCR signaling.

References

Jan 1, 1996·Methods in Enzymology·J C Wootton, S Federhen
Dec 5, 1998·Biochimica Et Biophysica Acta·M P Wymann, L Pirola
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Michael HanniganChi-Kuang Huang
Apr 5, 2003·Annual Review of Biochemistry·Gary M Bokoch
Sep 10, 2003·The International Journal of Biochemistry & Cell Biology·Verena Niggli
Jul 9, 2004·Biochimica Et Biophysica Acta·Andrew R Cross, Anthony W Segal
Dec 24, 2004·Molecular Biology of the Cell·Ting-Kuang NiuCatherine L Jackson
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Crislyn D'Souza-Schorey, Philippe Chavrier
May 18, 2007·Annual Review of Cell and Developmental Biology·Alison K Gillingham, Sean Munro
Dec 21, 2007·Molecular Biology of the Cell·Hajime YanoHisataka Sabe

❮ Previous
Next ❯

Citations

Apr 15, 2014·Cellular and Molecular Life Sciences : CMLS·John WrightElizabeth Sztul
Jul 15, 2015·Cellular Signalling·Fuguo ZhouGuangyu Wu
Dec 17, 2014·Biochimica Et Biophysica Acta·P T Hawkins, L R Stephens
Jan 7, 2016·American Journal of Respiratory and Critical Care Medicine·Dandi QiaoUNKNOWN COPDGene Investigators
Nov 27, 2015·Journal of Immunology Research·Jouda GamaraSylvain G Bourgoin
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Anupama HemalathaSatyajit Mayor
Oct 7, 2017·Biology of the Cell·Beata KaczmarekCatherine L Jackson
Feb 26, 2019·FEBS Letters·Yuichi MazakiSoichi Miwa
May 16, 2019·Molecular Biology of the Cell·Elizabeth SztulRichard A Kahn
Oct 4, 2017·Cell Communication and Signaling : CCS·Yuichi MazakiHisataka Sabe
Jul 10, 2019·Annual Review of Cell and Developmental Biology·Joseph Jose ThottacherrySatyajit Mayor
Jan 24, 2018·Journal of Cell Science·Justyna M MeissnerElizabeth Sztul
Sep 10, 2019·Frontiers in Cell and Developmental Biology·Jaakko Saraste, Kristian Prydz
May 15, 2013·Journal of Leukocyte Biology·Laure Gambardella, Sonja Vermeren
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Fernando Montaño-RendónGlenn F W Walpole
Aug 15, 2013·Journal of Cell Science·Samuel BouvetCatherine L Jackson
Jul 1, 2021·Molecular Biology of the Cell·Lucas C KlemmAnna Huttenlocher

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
GTPases
transfections
electrophoresis
pull-down
filter binding

Software Mentioned

ImageJ
AxioVision

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.