SFB 894:  Ca2+-Signalling: Molecular Mechanisms and Integrative Functions

• Subject Area: Medicine ; Biology
• Term: from 2011 to 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 157660137

Calcium signals are among the most important chemical cues in any eukaryotic cell. They underlie signal transduction pathways, which in turn regulate the release of neurotransmitters from neurons, of hormones from exocrine and neuroendocrine cells, the contraction of muscle cells, gene transcription and fertilization. In addition, the calcium ion is an important cofactor for many enzymes within and outside the cell. Extracellular calcium (2.1 to 2.6 mM) is decisive for formation and remodeling of teeth and bone, and it is indispensable for membrane excitability. Calcium ions are transported through the bloodstream and enter the cell via ion channels and exchangers. Within the cell, the cytosolic free calcium concentration (50 to 150 nM) is maintained by calcium binding proteins and clearance mechanisms transporting calcium ions out of the cell and into intracellular compartments like the endoplasmic reticulum or the mitochondria. Upon cell stimulation, the cytosolic free calcium increases by calcium entry through plasma membrane ion channels or by release of calcium stored in cellular compartments. The emerging calcium signals are spatially restricted to microdomains. Specifically, local calcium signals are dynamically controlled by transient membrane contacts of the endoplasmic reticulum and the plasma membrane or mitochondria mediated by various protein tethers. Local calcium signals then either lead to equally spatially restricted events, e.g. fusion of vesicles in presynaptic active zones, or propagate in a temporally encoded manner to other subcellular areas or even other cells, e.g. calcium waves in astrocytes.Since its start in 2011, the CRC 894 is investigating calcium signals from two different angles. On one side, we focus on the generation and spatial-temporal propagation of “elementary Ca2+ signals”, which induce molecular and cellular processes in confined environments like the synapse of neurons and immune cells or the areas surrounding calcium release channels of the endoplasmic reticulum. On the other hand, using cell and animal models, we investigate mechanisms by which these molecular events trigger changes of cell, organ and body functions. Only by pursuing experiments which combine pharmacological, electrophysiological, molecular-cellular and genetic approaches with animal models, their detailed phenotyping and ex vivo preparations from these models we will be able to get mechanistic insight and to fully comprehend the physiological and pathophysiological implications of calcium signals.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Ca2+-dependent CTL and NK cell cytotoxicity (Project Head Hoth, Markus )
• A02 - Physiological functions of novel STIM1 and STIM2 splice variants (Project Head Niemeyer, Ph.D., Barbara Anne )
• A03 - Cavβ2- and Cavβ3-specific signal transduction (Project Heads Belkacemi, Anouar ;  Flockerzi, Veit ;  Philipp, Stephan E. )
• A04 - Mechanisms and regulation of Ca2+ leakage from the ER (Project Heads Cavalié, Adolfo ;  Lang, Sven ;  Zimmermann, Richard )
• A05 - Structures and Mechanisms of Action of Succinate: Quinone Oxidoreductases and of Proteins Associated with Ca2+ Signaling (Project Head Lancaster, Roy )
• A06 - Functional properties of TRPM1 and TRPM3 membrane channel proteins in retinal bipolar cells (Project Head Oberwinkler, Johannes )
• A07 - Ca2+-dependent vesicle trafficking in the photoreceptor synapse (Project Head Schmitz, Frank )
• A08 - Ca2+ channel complexes in the cochlea synaptopathy (Project Head Engel, Jutta )
• A09 - CAPS function in dorsal root ganglion neurons (Project Head Becherer, Ph.D., Ute )
• A10 - Cytotoxic T lymphocyte function in vitro and in vivo (Project Heads Pattu, Varsha ;  Rettig, Jens )
• A11 - Complexin and synaptotagmin in Ca2+-triggered exocytosis (Project Head Bruns, Dieter )
• A12 - Neurotransmitter receptors and Ca2+ signals in cerebellar Bergmann glia (Project Heads Kirchhoff, Frank ;  Lauterbach, Marcel )
• A13 - Integrative consequences of defective mitochondrial Ca2+ uptake in Barth syndrome (Project Heads Maack, Christoph ;  Prates Roma, Ph.D., Leticia )
• A14 - Ca2+ channels in micro- and macroglial cells (Project Heads Beck, Andreas ;  Flockerzi, Veit )
• A15 - The membrane proteins TMEM1, 2 and 4 (Project Head Freichel, Marc )
• A16 - Function and regulation of Ca2+ signals in identified hypothalamic neurons (Project Head Leinders-Zufall, Trese )
• A17 - Mechanisms of receptor-operated Ca2+ signals in pheromone-detecting sensory neurons (Project Heads Leinders-Zufall, Trese ;  Zufall, Frank )
• A18 - Ca2+ signal generation in gonadotropes (Project Head Boehm, Ulrich )
• A19 - The role of Gq-dependent signaling for pacemaking, impulse propagation and contractility of the heart (Project Head Lipp, Ph.D., Peter )
• A20 - Mitochondrial membrane scaffolds as central nodes of intracellular Ca2+ signaling (Project Head van der Laan, Martin )
• A21 - Activation of the unfolded protein response of the endoplasmic reticulum (UPRER) by aberrant Ca2+ signals (Project Head Ernst, Robert )
• A22 - Mechanisms of calcium homeostasis and signal integration in primary cilia (Project Head Mick, David )
• P01 - Light nanoscopy (Project Heads Krause, Elmar ;  Rettig, Jens )
• P02 - Transgenic technologies (Project Heads Boehm, Ulrich ;  Weißgerber, Petra )
• P03 - Peptides and antibodies (Project Head Jung, Martin )
• Z - Central Tasks of the Collaborative Research Center (Project Heads Flockerzi, Veit ;  Rettig, Jens )

• Applicant Institution: Universität des Saarlandes
• Participating University: Julius-Maximilians-Universität Würzburg
• Spokespersons: Professor Dr. Veit Flockerzi, since 3/2021; Professor Dr. Jens Rettig, until 3/2021