FRET biosensors reveal AKAP-mediated shaping of subcellular PKA activity and a novel mode of Ca(2+)/PKA crosstalk

Cellular Signalling
Micah B SchottBryon Grove

Abstract

Scaffold proteins play a critical role in cellular homeostasis by anchoring signaling enzymes in close proximity to downstream effectors. In addition to anchoring static enzyme complexes, some scaffold proteins also form dynamic signalosomes that can traffic to different subcellular compartments upon stimulation. Gravin (AKAP12), a multivalent scaffold, anchors PKA and other enzymes to the plasma membrane under basal conditions, but upon [Ca(2+)]i elevation, is rapidly redistributed to the cytosol. Because gravin redistribution also impacts PKA localization, we postulate that gravin acts as a calcium "switch" that modulates PKA-substrate interactions at the plasma membrane, thus facilitating a novel crosstalk mechanism between Ca(2+) and PKA-dependent pathways. To assess this, we measured the impact of gravin-V5/His expression on compartmentalized PKA activity using the FRET biosensor AKAR3 in cultured cells. Upon treatment with forskolin or isoproterenol, cells expressing gravin-V5/His showed elevated levels of plasma membrane PKA activity, but cytosolic PKA activity levels were reduced compared with control cells lacking gravin. This effect required both gravin interaction with PKA and localization at the plasma membrane. Pre...Continue Reading

References

Apr 24, 2001·Journal of Vascular Research·B D Grove, A K Bruchey
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·J ZhangR Y Tsien
Feb 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hewang LiMartha Vaughan
Nov 5, 2003·The Journal of Biological Chemistry·Eun-Young AhnJay M McDonald
Dec 2, 2004·Nature Reviews. Molecular Cell Biology·Wei Wong, John D Scott
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Alan K HoweBrian P Hogan
Mar 1, 2006·European Journal of Cell Biology·Mark L Dell'AcquaLisa L Gomez
Mar 3, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karen E SmithMark L Dell'Acqua
Apr 28, 2006·The EMBO Journal·Debbie WilloughbyDermot M F Cooper
Jun 10, 2006·The Journal of Biological Chemistry·Jiangchuan TaoCraig C Malbon
Aug 10, 2006·Biochemical and Biophysical Research Communications·Michael D Allen, Jin Zhang
Feb 13, 2009·Experimental Cell Research·Xiaohong YanBryon Grove
Apr 4, 2009·Physiological Reviews·Shuiping DaiJohannes W Hell
Dec 23, 2009·Biochimica Et Biophysica Acta·David A Brown, David I Yule
May 11, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Qing-Hai YouQing-Li Luo
Sep 15, 2010·Molecular BioSystems·Charlene DepryJin Zhang
Dec 3, 2010·Cold Spring Harbor Perspectives in Biology·Michelle L Halls, Dermot M F Cooper
Apr 2, 2011·PloS One·Melanie J MorrisMarco G Casarotto
May 10, 2011·Science·Matthew C GoodWendell A Lim
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xinxin GaoJin Zhang
Dec 24, 2011·Experimental & Molecular Medicine·Hyouk-Bum KwonKyu-Won Kim
Jan 18, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Bettina BurnworthPeter J Nelson
Nov 2, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Seth F OliveriaWilliam A Sather
Dec 15, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Robbert HavekesTed Abel
Sep 14, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas WeissmüllerSean P Colgan
Feb 26, 2014·The Journal of General Physiology·Matthew D FullerWilliam A Catterall
Apr 23, 2014·PloS One·Shailesh R AgarwalRobert D Harvey

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