Identification of Cav2-PKCβ and Cav2-NOS1 complexes as entities for ultrafast electrochemical coupling

Proceedings of the National Academy of Sciences of the United States of America
Cristina E ConstantinBernd Fakler

Abstract

Voltage-activated calcium (Cav) channels couple intracellular signaling pathways to membrane potential by providing Ca2+ ions as second messengers at sufficiently high concentrations to modulate effector proteins located in the intimate vicinity of those channels. Here we show that protein kinase Cβ (PKCβ) and brain nitric oxide synthase (NOS1), both identified by proteomic analysis as constituents of the protein nano-environment of Cav2 channels in the brain, directly coassemble with Cav2.2 channels upon heterologous coexpression. Within Cav2.2-PKCβ and Cav2.2-NOS1 complexes voltage-triggered Ca2+ influx through the Cav channels reliably initiates enzymatic activity within milliseconds. Using BKCa channels as target sensors for nitric oxide and protein phosphorylation together with high concentrations of Ca2+ buffers showed that the complex-mediated Ca2+ signaling occurs in local signaling domains at the plasma membrane. Our results establish Cav2-enzyme complexes as molecular entities for fast electrochemical coupling that reliably convert brief membrane depolarization into precisely timed intracellular signaling events in the mammalian brain.

References

Oct 12, 1999·The Journal of Physiology·G P AhernM B Jackson
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Michael J BerridgeH Llewelyn Roderick
Oct 3, 2003·Nature·Xiang Dong TangToshinori Hoshi
Oct 15, 2003·Neuron·George J AugustineKeiko Tanaka
Feb 3, 2005·The Journal of General Physiology·Guangping Zhang, Frank T Horrigan
Jun 16, 2005·The Journal of General Physiology·Frank T HorriganToshinori Hoshi
Aug 17, 2005·Current Topics in Medicinal Chemistry·Gregory R J Thatcher
Sep 17, 2005·Circulation Research·Jonathan H JaggarCharles W Leffler
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Moritoshi SatoYoshio Umezawa
Feb 22, 2007·Journal of Cell Science·David J LoaneNeil V Marrion
May 5, 2007·The Journal of Biological Chemistry·Jin LiuDejian Ren
Nov 10, 2007·Biochemical and Biophysical Research Communications·Ji-Yoen Kim, Chul-Seung Park
Jun 25, 2008·Molecular & Cellular Proteomics : MCP·Jiusheng YanJames S Trimmer
Aug 15, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Henrike Berkefeld, Bernd Fakler
Sep 27, 2008·Neuron·Bernd Fakler, John P Adelman
Dec 18, 2008·Handbook of Experimental Pharmacology·Ian L Megson, Mark R Miller
Apr 14, 2009·Nature Neuroscience·William N GrimesJeffrey S Diamond
Jul 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Catrin Swantje MüllerUwe Schulte
Oct 21, 2010·Physiological Reviews·Henrike BerkefeldUwe Schulte
Apr 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Henrike Berkefeld, Bernd Fakler
Jul 28, 2015·Biochemistry·Tatyana I Igumenova
Nov 26, 2015·Molecular & Cellular Proteomics : MCP·Catrin S MüllerUwe Schulte

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Citations

Jan 7, 2019·Pflügers Archiv : European journal of physiology·Robert MallmannLubica Lacinova

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