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FASEB J. 2016 May;30(5):1958-67. doi: 10.1096/fj.201500140. Epub 2016 Feb 9.

RNA-induced silencing attenuates G protein-mediated calcium signals.

Author information

1
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA;
2
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA; Department of Biological Sciences, Queensborough Community College, Bayside, New York, USA; and.
3
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA; Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA sfscarlata@wpi.edu.

Abstract

Phospholipase Cβ (PLCβ) is activated by G protein subunits in response to environmental stimuli to increase intracellular calcium. In cells, a significant portion of PLCβ is cytosolic, where it binds a protein complex required for efficient RNA-induced silencing called C3PO (component 3 promoter of RISC). Binding between C3PO and PLCβ raises the possibility that RNA silencing activity can affect the ability of PLCβ to mediate calcium signals. By use of human and rat neuronal cell lines (SK-N-SH and PC12), we show that overexpression of one of the main components of C3PO diminishes Ca(2+) release in response to Gαq/PLCβ stimulation by 30 to 40%. In untransfected SK-N-SH or PC12 cells, the introduction of siRNA(GAPDH) [small interfering RNA(glyceraldehyde 3-phosphate dehydrogenase)] reduces PLCβ-mediated calcium signals by ∼30%, but addition of siRNA(Hsp90) (heat shock protein 90) had little effect. Fluorescence imaging studies suggest an increase in PLCβ-C3PO association in cells treated with siRNA(GAPDH) but not siRNA(Hsp90). Taken together, our studies raise the possibility that Ca(2+) responses to extracellular stimuli can be modulated by components of the RNA silencing machinery.-Philip, F., Sahu, S., Golebiewska, U., Scarlata, S. RNA-induced silencing attenuates G protein-mediated calcium signals.

KEYWORDS:

G protein signaling; calcium signaling; phospholipase Cβ

PMID:
26862135
PMCID:
PMC4836372
DOI:
10.1096/fj.201500140
[Indexed for MEDLINE]
Free PMC Article

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