G-protein-activated phospholipase C-beta, new partners for cell polarity proteins Par3 and Par6.
Cell polarity and asymmetric cell division are fundamental traits of all living cells and play an essential role in embryonic development, neuronal cell chirality formation, and maintenance of mammalian epithelial cell morphology. Heterotrimeric GTP-binding proteins (G proteins) are involved in directing cell polarity and asymmetric cell division in different organisms. However, the mechanism for G-protein-mediated cell polarity and asymmetric cell division is poorly understood. In this study, we have demonstrated that G-protein-activated phospholipase C-beta (PLC-beta) interacts with cell polarity proteins Par3 and Par6 (Par: partition-defective) to form protein complexes and to mediate downstream signal transduction. The interactions between PLC-beta and Par proteins are direct and require the extreme C-terminal-specific sequence motifs of PLC-beta and the PDZ (PSD95/Dlg/ZO-1) domains of Par proteins. Binding of Par proteins with PLC-beta stimulates PLC-beta enzymatic activity, leading to the hydrolysis of phosphatidylinositol-4,5-bisphosphate, and the production of diacylglycerol and inositol 1,4,5-triphosphate, important mediators in cell polarity and cell asymmetric division processes. Furthermore, we have shown that coexpression of PLC-beta with Par proteins induces transcriptional activation coupled to intracellular Ca2+ and the Wnt signaling pathway. Therefore, our data suggest that the interaction of PLC-beta with cell polarity Par proteins may serve as a nexus to transduce extracellular signals to transcriptional regulation through G-protein-mediated signaling pathway in cell polarity and cell asymmetric division.
Cai
Yi
Y
Department of Medical Biochemistry and Genetics, Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030, USA.
Stafford
Lewis J
LJ
Bryan
Brad A
BA
Mitchell
Dianne
D
Liu
Mingyao
M
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000096:biosynthesis / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D054799:Phospholipase C beta; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007527:Isoenzymes; C499657:PARD6A protein, human; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins