Jump to main content
Jump to site search

Issue 11, 2015
Previous Article Next Article

Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation

Author affiliations


Many biological processes are rhythmic and proper timing is increasingly appreciated as being critical for development and maintenance of physiological functions. To understand how temporal modulation of an input signal influences downstream responses, we employ microfluidic pulsatile stimulation of a G-protein coupled receptor, the muscarinic M3 receptor, in single cells with simultaneous real-time imaging of both intracellular calcium and NFAT nuclear localization. Interestingly, we find that reduced stimulation with pulses of ligand can give more efficient transcription factor activation, if stimuli are timed appropriately. Our experiments and computational analyses show that M3 receptor-induced calcium oscillations form a low pass filter while calcium-induced NFAT translocation forms a high pass filter. The combination acts as a band-pass filter optimized for intermediate frequencies of stimulation. We demonstrate that receptor desensitization and NFAT translocation rates determine critical features of the band-pass filter and that the band-pass may be shifted for different receptors or NFAT dynamics. As an example, we show that the two NFAT isoforms (NFAT4 and NFAT1) have shifted band-pass windows for the same receptor. While we focus specifically on the M3 muscarinic receptor and NFAT translocation, band-pass processing is expected to be a general theme that applies to multiple signaling pathways.

Graphical abstract: Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation

Back to tab navigation

Supplementary files

Article information

21 Jul 2015
04 Sep 2015
First published
08 Sep 2015

Integr. Biol., 2015,7, 1378-1386
Article type
Author version available

Search articles by author