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Molecular Neurophysiology

 

 

Nat Neurosci. 2017 Sep 25. doi: 10.1038/nn.4647. [Epub ahead of print]

Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways.
Schwarz Y.(1), Zhao N.(2), Kirchhoff F.(2), Bruns D(1).

 


Author information

1 Molecular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany.
2 Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany.


Abstract
Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes synaptic signaling, while synaptobrevin II-dependent glutamate release from astrocytes enhances synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites, elucidating new avenues of communication between astrocytes and neurons.
PMID:28945220
DOI:10.1038/nn.4647

EMBO J. 2017 Sep 15;36(18):2770-2789. doi: 10.15252/embj.201696369. Epub 2017 Aug 8.

Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory.

Bröker-Lai J1, Kollewe A2, Schindeldecker B3, Pohle J1,4, Nguyen Chi V5, Mathar I1, Guzman R3, Schwarz Y3, Lai A1, Weißgerber P6, Schwegler H7, Dietrich A8, Both M5, Sprengel R9, Draguhn A5, Köhr G4, Fakler B2,10, Flockerzi V6, Bruns D3, Freichel M11.

Author information
Abstract

Canonical transient receptor potential (TRPC) channels influence various neuronal functions. Using quantitative high-resolution mass spectrometry, we demonstrate that TRPC1, TRPC4, and TRPC5 assemble into heteromultimers with each other, but not with other TRP family members in the mouse brain and hippocampus. In hippocampal neurons from Trpc1/Trpc4/Trpc5-triple-knockout (Trpc1/4/5-/-) mice, lacking any TRPC1-, TRPC4-, or TRPC5-containing channels, action potential-triggered excitatory postsynaptic currents (EPSCs) were significantly reduced, whereas frequency, amplitude, and kinetics of quantal miniature EPSC signaling remained unchanged. Likewise, evoked postsynaptic responses in hippocampal slice recordings and transient potentiation after tetanic stimulation were decreased. In vivo, Trpc1/4/5-/- mice displayed impaired cross-frequency coupling in hippocampal networks and deficits in spatial working memory, while spatial reference memory was unaltered. Trpc1/4/5-/- animals also exhibited deficiencies in adapting to a new challenge in a relearning task. Our results indicate the contribution of heteromultimeric channels from TRPC1, TRPC4, and TRPC5 subunits to the regulation of mechanisms underlying spatial working memory and flexible relearning by facilitating proper synaptic transmission in hippocampal neurons.
© 2017 The Authors.KEYWORDS:
TRPC1/C4/C5 heteromeric assembly; cross‐frequency coupling; hippocampal synaptic transmission; relearning; spatial working memory
PMID:28790178
DOI:10.15252/embj.201696369 

Pflugers Arch. 2017 Sep 8. doi: 10.1007/s00424-017-2066-z. [Epub ahead of print]

v-SNARE function in chromaffin cells.

 

 

Author information

Abstract

Vesicle fusion is elementary for intracellular trafficking and release of signal molecules, thus providing the basis for diverse forms of intercellular communication like hormonal regulation or synaptic transmission. A detailed characterization of the mechanisms underlying exocytosis is key to understand how the nervous system integrates information and generates appropriate responses to stimuli. The machinery for vesicular release employs common molecular players in different model systems including neuronal and neuroendocrine cells, in particular members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein family, Sec1/Munc18-like proteins, and other accessory factors. To achieve temporal precision and speed, excitable cells utilize specialized regulatory proteins like synaptotagmin and complexin, whose interplay putatively synchronizes vesicle fusion and enhances stimulus-secretion coupling. In this review, we aim to highlight recent progress and emerging views on the molecular mechanisms, by which constitutively forming SNAREpins are organized in functional, tightly regulated units for synchronized release. Specifically, we will focus on the role of vesicle associated membrane proteins, also referred to as vesicular SNAREs, in fusion and rapid cargo discharge. We will further discuss the functions of SNARE regulators during exocytosis and focus on chromaffin cell as a model system of choice that allows for detailed structure-function analyses and direct measurements of vesicle fusion under precise control of intracellular [Ca]i.

KEYWORDS:

Ca2+-triggered exocytosis; Exocytosis; Membrane fusion; SNARE proteins; SNARE regulators

PMID:28887593
DOI:10.1007/s00424-017-2066-z

Madhurima Dhara gewann den 2000 Euro dotieren Pagliarello - Studienpreis 2016

sowie den Dr. Eduard-Martin-Preis 2017

der Universitätsgesellschaft des Saarlandes

 

Sie wurde für ihre Promotionsarbeit" Role of v-SNARE transmembrane domain and of SNARE regulators in Ca 2+ -triggeres exocytosis" ausgezeichnet.

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