Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system

Xue, Mingshan; Stradomska, Alicja; Chen, Hongmei; Brose, Nils; Zhang, Weiqi; Rosenmund, Christian; Reim, Kerstin

doi:10.1073/pnas.0803012105

Cited by 126 publications

(174 citation statements)

References 34 publications

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“…This agrees with previous observations, showing that insertions of 12 or 24 aa between the SNARE domain and the TMD abolishes SybII's ability to support vesicle priming (Deák et al, 2006). Yet, it contrasts with observations for null mutants of Complexin or Synaptotagmin at hippocampal synapses, indicating that linker mutations do not interfere with binding of these proteins to the SNARE complex (Geppert et al, 1994;Xue et al, 2008). Since linker extensions do not perturb SNARE complex assembly (McNew et al, 1999;Deák et al, 2006), it is likely that efficient priming of synaptic vesicles demands, beside trans-SNARE complex formation, a tight molecular link between the SNARE domain and the TMD.…”

Section: Linkers Impair Priming and Stimulus Secretion Coupling Of Ssvscontrasting

confidence: 41%

SNARE Force Synchronizes Synaptic Vesicle Fusion and Controls the Kinetics of Quantal Synaptic Transmission

Guzman

Schwarz²,

Rettig³

et al. 2010

J. Neurosci.

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Neuronal communication relies on rapid and discrete intercellular signaling but neither the molecular mechanisms of the exocytotic machinery that define the timing of the action potential-evoked response nor those controlling the kinetics of transmitter release from single synaptic vesicles are known. Here, we investigate how interference with the putative force transduction between the complexforming SNARE (soluble N-ethylamide-sensitive factor attachment protein receptor) domain and the transmembrane anchor of synaptobrevin II (SybII) affects action potential-evoked currents and spontaneous, quantal transmitter release at mouse hippocampal synapses. The results indicate that SybII-generated membrane stress effectively determines the kinetics of the action potential-evoked response and show that SNARE force modulates the concentration profile of cleft glutamate by controlling the rate of transmitter release from the single synaptic vesicle. Thus, multiple SybII actions determine the exquisite temporal regulation of neuronal signaling.

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Section: Linkers Impair Priming and Stimulus Secretion Coupling Of Ssvscontrasting

confidence: 41%

SNARE Force Synchronizes Synaptic Vesicle Fusion and Controls the Kinetics of Quantal Synaptic Transmission

Guzman

Schwarz²,

Rettig³

et al. 2010

J. Neurosci.

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“…The activating function of complexin is conserved across all species (mammals, Drosophila, and C. elegans) and different types of Ca 2+ -triggered synaptic vesicle fusion studied to date (7,12,16,28,(34)(35)(36)(37)(51)(52)(53). Regulation of spontaneous release by complexin is less conserved among species and varies depending on experimental conditions: for example, in Drosophila spontaneous release increases with knockout of complexin (14,54).…”

Section: Discussionmentioning

confidence: 99%

C-terminal domain of mammalian complexin-1 localizes to highly curved membranes

Gong

Lai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In presynaptic nerve terminals, complexin regulates spontaneous "mini" neurotransmitter release and activates Ca 2+ -triggered synchronized neurotransmitter release. We studied the role of the C-terminal domain of mammalian complexin in these processes using singleparticle optical imaging and electrophysiology. The C-terminal domain is important for regulating spontaneous release in neuronal cultures and suppressing Ca 2+ -independent fusion in vitro, but it is not essential for evoked release in neuronal cultures and in vitro. This domain interacts with membranes in a curvature-dependent fashion similar to a previous study with worm complexin [Snead D, Wragg RT, Dittman JS, Eliezer D (2014) Membrane curvature sensing by the C-terminal domain of complexin. Nat Commun 5:4955]. The curvature-sensing value of the C-terminal domain is comparable to that of α-synuclein. Upon replacement of the C-terminal domain with membrane-localizing elements, preferential localization to the synaptic vesicle membrane, but not to the plasma membrane, results in suppression of spontaneous release in neurons. Membrane localization had no measurable effect on evoked postsynaptic currents of AMPA-type glutamate receptors, but mislocalization to the plasma membrane increases both the variability and the mean of the synchronous decay time constant of NMDA-type glutamate receptor evoked postsynaptic currents.

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“…Cplx3 expression in mouse brain is very low and does not contribute significantly to synaptic transmission in the brain regions tested so far (Xue et al, 2008). All four complexin isoforms are expressed in the retina, where Cplx1 and Cplx2 are found in conventional synapses of amacrine cells, whereas Cplx3 and Cplx4 are predominantly expressed in ribbon synapses of photoreceptors and bipolar cells (Reim et al, 2005).…”

Section: +mentioning

confidence: 96%

“…1C) (Reim et al, 2005). As we described previously, deletion of the Cplx3 gene leads to complete loss of Cplx3 protein in brain (Xue et al, 2008). Western blot analyses using extracts from adult retinae showed that expression of Cplx3 is abolished in homozygous Cplx3 knockouts (Fig.…”

Section: Generation Of Cplx4 Single-knockout Andmentioning

confidence: 96%

“…Their deletion in mice causes profound deficits in release probability, evoked transmitter release and reduced spontaneous release at neuronal synapses (Reim et al, 2001;Xue et al, 2007;Xue et al, 2008), as well as reduced secretory granule fusion in adrenal chromaffin cells (Cai et al, 2008), which indicates that complexins act as positive regulators at or following the Ca 2+ -triggering step of synaptic vesicle fusion. The notion that complexins act as facilitators of SNARE-mediated secretory vesicle fusion is also supported by the observation that overexpression of Cplx2 in wild-type chromaffin cells increases chromaffin granule secretion (Cai et al, 2008).…”

Section: +mentioning

confidence: 99%

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Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4

Reim

Regus-Leidig

Ammermüller

et al. 2009

Journal of Cell Science

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Complexins regulate the speed and Ca2+ sensitivity of SNARE-mediated synaptic vesicle fusion at conventional synapses. Two of the vertebrate complexins, Cplx3 and Cplx4, are specifically localized to retinal ribbon synapses. To test whether Cplx3 and Cplx4 contribute to the highly efficient transmitter release at ribbon synapses, we studied retina function and structure in Cplx3 and Cplx4 single- and double-knockout mice. Electroretinographic recordings from single and double mutants revealed a cooperative perturbing effect of Cplx3 and Cplx4 deletion on the b-wave amplitude, whereas most other detected effects in both plexiform synaptic layers were additive. Light and electron microscopic analyses uncovered a disorganized outer plexiform layer in the retinae of mice lacking Cplx3 and Cplx4, with a significant proportion of photoreceptor terminals containing spherical free-floating ribbons. These structural and functional aberrations were accompanied by behavioural deficits indicative of a vision deficit. Our results show that Cplx3 and Cplx4 are essential regulators of transmitter release at retinal ribbon synapses. Their loss leads to aberrant adjustment and fine-tuning of transmitter release at the photoreceptor ribbon synapse, alterations in transmission at bipolar cell terminals, changes in the temporal structure of synaptic processing in the inner plexiform layer of the retina and perturbed vision.

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Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system

Cited by 126 publications

References 34 publications

SNARE Force Synchronizes Synaptic Vesicle Fusion and Controls the Kinetics of Quantal Synaptic Transmission

SNARE Force Synchronizes Synaptic Vesicle Fusion and Controls the Kinetics of Quantal Synaptic Transmission

C-terminal domain of mammalian complexin-1 localizes to highly curved membranes

Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4

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