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.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:46 p.m.) |
Deposited | 2 years, 1 month ago (July 22, 2023, 7:38 a.m.) |
Indexed | 1 month, 3 weeks ago (July 8, 2025, 7:29 a.m.) |
Issued | 24 years, 3 months ago (May 14, 2001) |
Published | 24 years, 3 months ago (May 14, 2001) |
Published Online | 24 years, 3 months ago (May 14, 2001) |
Published Print | 24 years, 3 months ago (May 14, 2001) |
@article{Funamoto_2001, title={Role of Phosphatidylinositol 3′ Kinase and a Downstream Pleckstrin Homology Domain–Containing Protein in Controlling Chemotaxis inDictyostelium}, volume={153}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.153.4.795}, DOI={10.1083/jcb.153.4.795}, number={4}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Funamoto, Satoru and Milan, Kristina and Meili, Ruedi and Firtel, Richard A.}, year={2001}, month=may, pages={795–810} }