Temporal and spatial regulation of phosphoinositide signaling mediates cytokinesis.
Polarity is a prominent feature of both chemotaxis and cytokinesis. In chemotaxis, polarity is established by local accumulation of PI(3,4,5)P3 at the cell's leading edge, achieved through temporal and spatial regulation of PI3 kinases and the tumor suppressor, PTEN. We find that as migrating D. discoideum cells round up to enter cytokinesis, PI(3,4,5)P3 signaling is uniformly suppressed. Then, as the spindle and cell elongate, PI3 kinases and PTEN move to and function at the poles and furrow, respectively. Cell lines lacking both of these enzymatic activities fail to modulate PI(3,4,5)P3 levels, are defective in cytokinesis, and cannot divide in suspension. The cells continue to grow and duplicate their nuclei, generating large multinucleate cells. Furrows that fail to ingress between nuclei are unable to stably accumulate myosin filaments or suppress actin-filled ruffles. We propose that phosphoinositide-linked circuits, similar to those that bring about asymmetry during cell migration, also regulate polarity in cytokinesis.
Janetopoulos
Chris
C
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Borleis
Jane
J
Vazquez
Francisca
F
Iijima
Miho
M
Devreotes
Peter
P
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D002633:Chemotaxis; D048749:Cytokinesis / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D003598:Cytoskeletal Proteins; D005492:Folic Acid; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C118303:phosphoinositide-3,4,5-triphosphate; C494929:PTEN protein, human