Ca(2+) signaling; G-protein-coupled receptors; TRP; TRPC C; mass spectrometry; neurons; patch clamp; protein biochemistry; proteomics; transient receptor potential channels; General Neuroscience
Abstract :
[en] In the mammalian brain TRPC channels, a family of Ca2+-permeable cation channels, are involved in a variety of processes from neuronal growth and synapse formation to transmitter release, synaptic transmission and plasticity. The molecular appearance and operation of native TRPC channels, however, remained poorly understood. Here, we used high-resolution proteomics to show that TRPC channels in the rodent brain are macro-molecular complexes of more than 1 MDa in size that result from the co-assembly of the tetrameric channel core with an ensemble of interacting proteins (interactome). The core(s) of TRPC1-, C4-, and C5-containing channels are mostly heteromers with defined stoichiometries for each subtype, whereas TRPC3, C6, and C7 preferentially form homomers. In addition, TRPC1/C4/C5 channels may co-assemble with the metabotropic glutamate receptor mGluR1, thus guaranteeing both specificity and reliability of channel activation via the phospholipase-Ca2+ pathway. Our results unveil the subunit composition of native TRPC channels and resolve the molecular details underlying their activation.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kollewe, Astrid; Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany
Schwarz, Yvonne; Institute of Physiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany
Oleinikov, Katharina; Institute of Physiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany
Raza, Ahsan; Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland University, 66421 Homburg, Germany
Haupt, Alexander; Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany
Wartenberg, Philipp; Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland University, 66421 Homburg, Germany
Wyatt, Amanda; Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland University, 66421 Homburg, Germany
Boehm, Ulrich; Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland University, 66421 Homburg, Germany
Ectors, Fabien ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Bildl, Wolfgang; Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany
Zolles, Gerd; Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany
Schulte, Uwe; Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany, Signalling Research Centres BIOSS and CIBSS, Schänzlestr. 18, 79104 Freiburg, Germany
Bruns, Dieter; Institute of Physiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany
Flockerzi, Veit; Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland University, 66421 Homburg, Germany. Electronic address: veit.flockerzi@uks.eu
Fakler, Bernd ; Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany, Signalling Research Centres BIOSS and CIBSS, Schänzlestr. 18, 79104 Freiburg, Germany, Center for Basics in NeuroModulation, Breisacherstr. 4, 79106 Freiburg, Germany. Electronic address: bernd.fakler@physiologie.uni-freiburg.de
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