SNAP-25 Modulation of Calcium Dynamics Underlies Differences in GABAergic and Glutamatergic Responsiveness to Depolarization

Verderio, Claudia; Pozzi, Davide; Pravettoni, Elena; Inverardi, Francesca; Schenk, Ursula; Coco, Silvia; Proux-Gillardeaux, Véronique; Galli, Thierry; Rossetto, Ornella; Frassoni, Carolina; Matteoli, Michela

doi:10.1016/s0896-6273(04)00077-7

Cited by 198 publications

(179 citation statements)

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“…These data agree with the assumption that the SNARE mechanisms largely characterize the excitatory synapses and that glutamate-containing vesicles release their content via SNARE-dependent mechanisms [12,15,33,34]. However, this study demonstrates subpopulations of glutamatergic synapses in the cerebellar cortex that do not contain the examined SNARE proteins.…”

Section: Discussionsupporting

confidence: 89%

“…This observation largely agrees with the assumption that SNAP-25 independent exocytotic pathways exist to support neurotransmission in GABAergic synapses [12,33], even if this assumption is not accepted by some researchers [14]. Moreover, it should again pointed out that some GABAergic axon terminals of basket neurons are exceptions to this assumption.…”

Section: Discussionsupporting

confidence: 84%

“…In particular, specific sets of SNARE proteins seem to be required to regulate trafficking of vesicles containing different types of neurotransmitters, possibly even one set per neurotransmitter [30,31]. According to this hypothesis, scholars have reported that SNARE proteins are strongly expressed in excitatory (glutamatergic) synapses and may be lacking in inhibitory (GABAergic) synapses [12,15,32-34]. …”

Section: Introductionmentioning

confidence: 99%

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VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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BackgroundThe aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1.ResultsThe examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2) and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively). The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons.ConclusionThe present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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“…56 By taking advantage of mixed cultures of wt and Het neurons, we demonstrated that postsynaptic defects in In recent years SNARE/SM proteins have been shown to be involved in activity-dependent AMPA receptor exocytosis during LTP 22 and SNAP-25, in particular, has been reported to have a role in the removal of kainate receptors from the postsynaptic membrane, 57 in the insertion of NMDA receptors in neuronal plasma membrane 21 and of P/Q and L typevoltage gated calcium channels. 10,58 Also, acute regulation of SNAP-25 expression has been found to impair synaptic plasticity probably affecting NMDAR trafficking. 22 Our data indicate that SNAP-25 has also a structural role in the postsynaptic compartment by interacting with the postsynaptic protein p140Cap, which in turn binds to PSD-95.…”

Section: Discussionmentioning

confidence: 99%

Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

et al. 2015

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Impairment of synaptic function can lead to neuropsychiatric disorders collectively referred to as synaptopathies. The SNARE protein SNAP-25 is implicated in several brain pathologies and, indeed, brain areas of psychiatric patients often display reduced SNAP-25 expression. It has been recently found that acute downregulation of SNAP-25 in brain slices impairs long-term potentiation; however, the processes through which this occurs are still poorly defined. We show that in vivo acute downregulation of SNAP-25 in CA1 hippocampal region affects spine number. Consistently, hippocampal neurons from SNAP-25 heterozygous mice show reduced densities of dendritic spines and defective PSD-95 dynamics. Finally, we show that, in brain, SNAP-25 is part of a molecular complex including PSD-95 and p140Cap, with p140Cap being capable to bind to both SNAP-25 and PSD-95. These data demonstrate an unexpected role of SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels -as occurring in schizophrenia -may contribute to the pathology through an effect on postsynaptic function and plasticity. Cell Death and Differentiation (2015) 22, 1425-1436 doi:10.1038/cdd.2014 published online 13 February 2015 Synapses are complex cellular junctions specialized for communication between neurons. Epidemiological and genetic studies demonstrated that deficiencies in synapse function 1 are implicated in a wide range of brain disorders, including neurodegenerative 2 and psychiatric diseases such as schizophrenia 3,4 and autism. 5,6 A hallmark of synaptic specializations is their dependence on highly organized complexes of proteins that interact with each other. Therefore, the loss or modification of key synaptic proteins might directly affect the properties of such networks and, ultimately, synaptic function.SNAP-25 is a component of the SNARE complex, which is central to synaptic vesicle exocytosis 7,8 and which has a role in the regulation of voltage-gated calcium channels. 9,10 The SNAP25 gene has been associated with attention deficit hyperactivity disorder (ADHD) 11,12 and with schizophrenia. 13,14 Consistently, SNAP-25 levels are lower in the hippocampus 15 and in the frontal lobe 16 of patients with schizophrenia. DNA variants of the SNAP25 gene that associate with ADHD are also associated with reduced expression level of the transcript in prefrontal cortex. 17 Finally, reduction of SNAP-25 levels has been found to cause neurodegeneration in mice lacking the synaptic vesicle protein Cysteine-string protein-α, possibly due to the impaired SNARE-complex assembly produced by the decreased SNAP-25. 18 The mechanisms by which reduced SNAP-25 expression may result in a psychiatric disease are still undefined, although alterations in neurotransmitter release have been indicated as potential causative processes. 19,20 Recently an unexpected postsynaptic role of SNAP-25 has been described, with the protein controlling NMDA and kainate receptor trafficking. 21 Furthermore, it has been lately ...

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“…Reducing the calcium levels by chelators induces a higher sensitivity of GABA-ergic neurons to BoNT/A action (Grumelli et al, 2010;Verderio et al, 2004).…”

Section: Preferential Effect On Excitatory Vs Inhibitory Neuronsmentioning

confidence: 99%