SFB 1381 logo CIBBS
FOR2143 logo FOR5159 logo
euSNN logo

Institute of Physiology
University of Freiburg
Hermann-Herder-Str. 7
79104 Freiburg
Germany
How to find us

 

Physiology I
Prof. Dr. Marlene Bartos
Tel.: +49 (0)761 203 5194
Fax.: +49 (0)761 203 5204

 

Physiology II
Prof. Dr. Bernd Fakler
Tel. +49 761 203-5176
Fax +49 761 203-5191
[JavaScript Protected Email]

Uni-Logo
You are here: Home News Identification of Cav2-PKCβ and Cav2-NOS1 complexes as entities for ultrafast electrochemical coupling
Document Actions

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

Constantin CE, Müller CS, Leitner MG, Bildl W, Schulte U, Oliver D, Fakler B, PNAS 2017 May 30;114(22):5707-5712. doi: 10.1073/pnas.1616394114

May 18, 2017

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

Personal tools