RRC ID 29027
Author Funamoto S, Milan K, Meili R, Firtel RA.
Title Role of phosphatidylinositol 3' kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in dictyostelium.
Journal J Cell Biol
Abstract We show that cells lacking two Dictyostelium class I phosphatidylinositol (PI) 3' kinases (PI3K and pi3k1/2-null cells) or wild-type cells treated with the PI3K inhibitor LY294002 are unable to properly polarize, are very defective in the temporal, spatial, and quantitative regulation of chemoattractant-mediated filamentous (F)-actin polymerization, and chemotax very slowly. PI3K is thought to produce membrane lipid-binding sites for localization of PH domain-containing proteins. We demonstrate that in response to chemoattractants three PH domain-containing proteins do not localize to the leading edge in pi3k1/2-null cells, and the translocation is blocked in wild-type cells by LY294002. Cells lacking one of these proteins, phdA-null cells, exhibit defects in the level and kinetics of actin polymerization at the leading edge and have chemotaxis phenotypes that are distinct from those described previously for protein kinase B (PKB) (pkbA)-null cells. Phenotypes of PhdA-dominant interfering mutations suggest that PhdA is an adaptor protein that regulates F-actin localization in response to chemoattractants and links PI3K to the control of F-actin polymerization at the leading edge during pseudopod formation. We suggest that PKB and PhdA lie downstream from PI3K and control different downstream effector pathways that are essential for proper chemotaxis.
Volume 153(4)
Pages 795-810
Published 2001-5-14
DOI 10.1083/jcb.153.4.795
PMID 11352940
PMC PMC2192389
MeSH Actins / metabolism Amino Acid Sequence Animals Blood Proteins / chemistry* Blood Proteins / genetics Chemotaxis / drug effects Chemotaxis / physiology* Chromones / pharmacology Dictyostelium / cytology* Dictyostelium / enzymology Enzyme Inhibitors / pharmacology Folic Acid Kinetics Microscopy, Video Molecular Sequence Data Morpholines / pharmacology Mutagenesis, Insertional / physiology Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Phosphoinositide-3 Kinase Inhibitors Phosphoproteins / chemistry* Phosphoproteins / genetics Polymers / metabolism Protein Structure, Tertiary Protein-Serine-Threonine Kinases* Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-akt Protozoan Proteins / chemistry Protozoan Proteins / genetics* Protozoan Proteins / metabolism
IF 8.811
Times Cited 188
Cellular slime molds S00007