Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis.
We have investigated the mechanisms of leading edge formation in chemotaxing Dictyostelium cells. We demonstrate that while phosphatidylinositol 3-kinase (PI3K) transiently translocates to the plasma membrane in response to chemoattractant stimulation and to the leading edge in chemotaxing cells, PTEN, a negative regulator of PI3K pathways, exhibits a reciprocal pattern of localization. By uniformly localizing PI3K along the plasma membrane, we show that chemotaxis pathways are activated along the lateral sides of cells and PI3K can initiate pseudopod formation, providing evidence for a direct instructional role of PI3K in leading edge formation. These findings provide evidence that differential subcellular localization and activation of PI3K and PTEN is required for proper chemotaxis.
Funamoto
Satoru
S
Section of Cell and Developmental Biology, Division of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093, USA.
Meili
Ruedi
R
Lee
Susan
S
Parry
Lisa
L
Firtel
Richard A
RA
D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics*; D002462:Cell Membrane / Q000201:enzymology / Q000648:ultrastructure; D016764:Cell Polarity / Q000235:genetics*; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000201:enzymology / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D007202:Indicators and Reagents; D007527:Isoenzymes; D008164:Luminescent Proteins; C428644:PhdA protein, Dictyostelium; D010716:Phosphatidylinositols; D015800:Protozoan Proteins; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; D018631:ras Proteins