Phospholipase C isoforms are localized at the cleavage furrow during cytokinesis.
It has recently been demonstrated that phosphatidylinositol 4,5-bisphosphate (PIP2) is localized at the cleavage furrow in dividing cells and its hydrolysis is required for complete cytokinesis, suggesting a pivotal role of PIP2 in cytokinesis. Here, we report that at least three mammalian isoforms of phosphoinositide-specific phospholipase C (PLC), PLCdelta1, PLCdelta3 and PLCbeta1, are localized to the cleavage furrow during cytokinesis. Targeting of the delta1 isoform to the furrow depends on the specific interaction between the PH domain and PIP2 in the plasma membrane. The necessity of active PLC in animal cell cytokinesis was confirmed using the specific inhibitors for PIP2 hydrolysis. These results support the model that activation of selected PLC isoforms at the cleavage furrow controls progression of cytokinesis through regulation of PIP2 levels: induction of the cleavage furrow by a contractile ring consisting of actomyosin is regulated by PIP2-dependent actin-binding proteins and formation of specific lipid domains required for membrane separation is affected by alterations in the lipid composition of the furrow.
Naito
Yoko
Y
Laboratory of Biological Signaling, Graduate School of Life Science, University of Hyogo, Harima Science Garden City, Hyogo 678-1297.
Okada
Masashi
M
Yagisawa
Hitoshi
H
D000818:Animals; D002460:Cell Line; D048749:Cytokinesis / Q000502:physiology*; D004285:Dogs; D004963:Estrenes / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D010742:Phospholipid Ethers / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004963:Estrenes; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010742:Phospholipid Ethers; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C026659:edelfosine; D010738:Type C Phospholipases; C518024:PLCD1 protein, human; C518028:PLCD3 protein, human; D054799:Phospholipase C beta; D054803:Phospholipase C delta; C518025:Plcd1 protein, mouse