Differential Abilities of SNAP-25 Homologs to Support Neuronal Function

Delgado‐Martínez, Ignacio; Nehring, Ralf B.; Sørensen, Jakob B.

doi:10.1523/jneurosci.5092-06.2007

Cited by 130 publications

(143 citation statements)

References 71 publications

(92 reference statements)

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“…SNAP-25 phosphorylation by Protein Kinase C (PKC) is of fundamental importance for the insertion of NMDA receptors in neuronal plasma membrane 7 . In line with the SNARE role in postsynaptic function, amplitude of mEPSCs was reported to be reduced in the absence of SNAP-25 46,47 , while exogenous expression of either SNAP-25a or SNAP-25b rescued the amplitude value 47 . Finally, a recent report showed that downregulation of the protein impairs potentiation phenomena 48 .…”

Section: Discussionmentioning

confidence: 60%

SNAP-25 regulates spine formation through postsynaptic binding to p140Cap

et al. 2013

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Synaptosomal-associated protein of 25 kDa (SNAP-25) is a member of the Soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNARE) protein family, required for exocytosis of synaptic vesicles and regulation of diverse ion channels. Here, we show that acute reduction of SNAP-25 expression leads to an immature phenotype of dendritic spines that are, consistently, less functional. Conversely, over-expression of SNAP-25 results in an increase in the density of mature, Postsynaptic Density protein 95 (PSD-95)-positive spines. The regulation of spine morphogenesis by SNAP-25 depends on the protein's ability to bind both the plasma membrane and the adaptor protein p140Cap, a key protein regulating actin cytoskeleton and spine formation. We propose that SNAP-25 allows the organization of the molecular apparatus needed for spine formation by recruiting and stabilizing p140Cap.

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Section: Discussionmentioning

confidence: 60%

SNAP-25 regulates spine formation through postsynaptic binding to p140Cap

et al. 2013

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“…These two isoforms diverge only for nine amino acids in a domain involved in membrane association and disassembly, after exocytosis, of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. [37][38][39] In individuals homozygous for the 'C' allele, we observed that only SNAP25b is significantly increased. Interestingly, in absence of this isoform, 75% of mice die before 5 weeks of age and surviving animals present alteration in synaptic maturation as well as deficit in synaptic transmission.…”

Section: Discussionmentioning

confidence: 64%

A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain

et al. 2009

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Bipolar disorder (BD) is one of the most common and persistent psychiatric disorders. Earlyonset BD has been shown to be the most severe and familial form. We recently carried out a whole-genome linkage analysis on sibpairs affected by early-onset BD and showed that the 20p12 region was more frequently shared in our families than expected by chance. The synaptosomal-associated protein SNAP25 is a presynaptic plasma membrane protein essential for the triggering of vesicular fusion and neurotransmitter release, and for which abnormal protein levels have been reported in postmortem studies of bipolar patients. We hypothesised that variations in the gene encoding SNAP25, located on chromosome 20p12, might influence the susceptibility to early-onset BD. We screened SNAP25 for mutations and performed a case-control association study in 197 patients with early-onset BD, 202 patients with late-onset BD and 136 unaffected subjects. In addition, we analysed the expression level of the two SNAP25 isoforms in 60 brains. We showed that one variant, located in the promoter region, was associated with early-onset BD but not with the late-onset subgroup. In addition, individuals homozygous for this variant showed a significant higher SNAP25b expression level in prefrontal cortex. These results show that variations in SNAP25, associated with an increased gene expression level in prefrontal cortex, might predispose to early-onset BD. Further analyses of this gene, as well as analysis of genes encoding for the SNAP25 protein partners, are required to understand the impact of such molecular mechanisms in BD.

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“…Based on this finding, Delgado-Martinez et al [12] suggested that the lower efficacy of BoNT/A in inhibiting GABAergic vesicle cycling might be attributable to the higher calcium responsiveness of GABAergic relative to glutamatergic neurons. Given SNAP-25 but not SNAP-25 negatively modulates evoked calcium responses [5], the possibility opens that SNAP-25 …”

Section: To Get Insights Into the Mechanisms By Which Overexpression mentioning

confidence: 99%

“…Indeed, although most cultured GABAergic neurons use SNAP-25 for evoked exocytosis [12,13,14], they are characterized by lower levels of SNAP-25 as compared to glutamatergic terminals [5,15,16,17] and become sensitive to BoNT/A upon exogenous expression of the protein [11]. Why BoNT/A is highly efficient in inhibiting vesicle cycling selectively in neurons expressing high levels of SNAP-25 is still to be defined.…”

Section: Introductionmentioning

confidence: 99%

Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations

et al. 2010

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SNAP-25 is a SNARE protein implicated in exocytosis and in the negative modulation of voltage gated calcium channels. We have previously shown that GABAergic synapses, which express SNAP-25 at much lower levels relative to glutamatergic ones, are characterized by a higher calcium responsiveness to depolarization and are largely resistant to botulinum toxin A. We show here that silencing of SNAP-25 in glutamatergic neurons, a procedure which increases KCl-induced calcium elevations, confers these synapses with toxin resistance. Since it is known that calcium reverts the efficacy of botulinum A, we investigated whether the lower effectiveness of the toxin in inhibiting GABAergic vesicle cycling might be attributable to higher evoked calcium transients of inhibitory neurons. We demonstrate that either expression of SNAP-25 or BAPTA/AM treatment, both inhibiting calcium dynamics, facilitate block of GABAergic vesicle exocytosis upon toxin treatment. These data indicate that intrinsic calcium dynamics control botulinum A susceptibility in distinct neuronal populations.

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Differential Abilities of SNAP-25 Homologs to Support Neuronal Function

Cited by 130 publications

References 71 publications

SNAP-25 regulates spine formation through postsynaptic binding to p140Cap

SNAP-25 regulates spine formation through postsynaptic binding to p140Cap

A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain

Intrinsic calcium dynamics control botulinum toxin A susceptibility in distinct neuronal populations

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