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Molecular Neurophysiology
to study
MOLECULAR MECHANISMS MEDIATING NEUROTRANSMITTER RELEASE
at the UNIVERSITY OF SAARLAND
(Homburg/Saar) Germany
Ph.D. positions are available to elucidate the molecular mechanisms that mediate neuronal exocytosis. Our goal is to define the molecular events that couple Ca2+ signaling to the release of neurotransmitter. We are addressing this problem with state-of-the-art molecular (knock-out mice),biochemical, electrophysiological and fluorescence microscopy techniques (e.g. carbon fiber amperometry, membrane capacitance measurements, Ca2+-imaging, SIM and STED microscopy). The work is directly supported by technical personnel and applicants are given the opportunity to extend their research interest internationally through project–oriented collaborations with groups in the USA. Applicants with a physical, biochemical or biological background are encouraged to apply.
Please send your curriculum vitae and a brief statement of research interest to: Prof. Dr. Dieter Bruns, Dept. of Physiology, Center of Integrated Physiology and Molecular Medicine, University of Saarland, 66421 Homburg, Building 48, Germany, Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Exemplary publications:
Schwarz Y, Oleinikov K, Schindeldecker B, Wyatt A, Weißgerber P, Flockerzi V, Boehm U, Freichel M, Bruns D (2019). TRPC channels regulate Ca2+-signaling and short-term plasticity of fast glutamatergic synapses. PLOS Biol., doi: 10.1371/journal.pbio.3000445
Makke M, Mantero Martinez M, Gaya S, Schwarz Y, Frisch W, Silva-Bermudez L, Jung M2, Mohrmann R, Dhara M, Bruns D (2018). A mechanism for exocytotic arrest by the Complexin C-terminus. Elife. doi: 10.7554/eLife.38981.
Dhara M, Mohrmann R, Bruns D (2018). v-SNARE function in chromaffin cells. Pflugers Arch., 470:169-180.
Schwarz Y, Zhao N, Kirchhoff F, Bruns D. (2017). Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways. Nat Neurosci.20:1529-1539.
PLoS Biol. 2019 Sep 19;17(9)
TRPC channels regulate Ca2+-signaling and short-term plasticity of fast glutamatergic synapses.
Schwarz Y, Oleinikov K, Schindeldecker B, Wyatt A, Weißgerber P, Flockerzi V, Boehm U, Freichel M, Bruns D.
Transient receptor potential (TRP) proteins form Ca2+-permeable, nonselective cation channels, but their role in neuronal Ca2+ homeostasis is elusive. In the present paper, we show that TRPC channels potently regulate synaptic plasticity by changing the presynaptic Ca2+-homeostasis of hippocampal neurons. Specifically, loss of TRPC1/C4/C5 channels decreases basal-evoked secretion, decreases the pool size of readily releasable vesicles, and accelerates synaptic depression during high-frequency stimulation (HFS). In contrast, primary TRPC5 channel-expressing neurons, identified by a novel TRPC5-τ-green fluorescent protein (τGFP) knockin mouse line, show strong short-term enhancement (STE) of synaptic signaling during HFS, indicating a key role of TRPC5 in short-term plasticity. Lentiviral expression of either TRPC1 or TRPC5 turns classic synaptic depression of wild-type neurons into STE, demonstrating that TRPCs are instrumental in regulating synaptic plasticity. Presynaptic Ca2+ imaging shows that TRPC activity strongly boosts synaptic Ca2+ dynamics, showing that TRPC channels provide an additional presynaptic Ca2+ entry pathway, which efficiently regulates synaptic strength and plasticity.
DOI
A mechanism for exocytotic arrest by the Complexin C-terminus.
ComplexinII (CpxII) inhibits non-synchronized vesicle fusion, but the underlying mechanisms have remained unclear. Here, we provide evidence that the far C-terminal domain (CTD) of CpxII interferes with SNARE assembly, thereby arresting tonic exocytosis. Acute infusion of a CTD-derived peptide into mouse chromaffin cells enhances synchronous release by diminishing premature vesicle fusion like full-length CpxII, indicating a direct, inhibitory function of the CTD that sets the magnitude of the primed vesicle pool. We describe a high degree of structural similarity between the CpxII CTD and the SNAP25-SN1 domain (C-terminal half) and show that the CTD peptide lowers the rate of SDS-resistant SNARE complex formation in vitro. Moreover, corresponding CpxII:SNAP25 chimeras do restore complexin's function and even 'superclamp' tonic secretion. Collectively, these results support a so far unrecognized clamping mechanism wherein the CpxII C-terminus hinders spontaneous SNARE complex assembly, enabling the build-up of a release-ready pool of vesicles for synchronized Ca2+-triggered exocytosis.
