title: Phospholipase Cβ connects G protein signaling with RNA interference.
abstract: Phosphoinositide-specific-phospholipase Cβ (PLCβ) is the main effector of Gαq stimulation which is coupled to receptors that bind acetylcholine, bradykinin, dopamine, angiotensin II as well as other hormones and neurotransmitters. Using a yeast two-hybrid and other approaches, we have recently found that the same region of PLCβ that binds Gαq also interacts with Component 3 Promoter of RNA induced silencing complex (C3PO), which is required for efficient activity of the RNA-induced silencing complex. In purified form, C3PO competes with Gαq for PLCβ binding and at high concentrations can quench PLCβ activation. Additionally, we have found that the binding of PLCβ to C3PO inhibits its nuclease activity leading to reversal of RNA-induced silencing of specific genes. In cells, we found that PLCβ distributes between the plasma membrane where it localizes with Gαq, and in the cytosol where it localizes with C3PO. When cells are actively processing small interfering RNAs the interaction between PLCβ and C3PO gets stronger and leads to changes in the cellular distribution of PLCβ. The magnitude of attenuation is specific for different silencing RNAs. Our studies imply a direct link between calcium responses mediated through Gαq and post-transcriptional gene regulation through PLCβ.
authors.affiliation: Dept. of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA; Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA. Electronic address: sfscarlata@wpi.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
authors.affiliation: Dept. of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA; Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Osama
authors.initials: O
authors.lastname: Garwain
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Williams
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA; Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU), Spain.
authors.forename: Imanol Gonzalez
authors.initials: IG
authors.lastname: Burguera
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosati
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Shriya
authors.initials: S
authors.lastname: Sahu
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
authors.forename: Finly
authors.initials: F
authors.lastname: Philip
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609, USA; Dept of Biological Sciences and Geology, Queensborough Community College, Bayside, NY 11364, USA.
authors.forename: Urszula
authors.initials: U
authors.lastname: Golebiewska
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D054799:Phospholipase C beta / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium
keywords: Calcium signaling; Component 3 promoter of RNA silencing; G protein signaling; Phospholipase Cβ; RNA silencing