Disease relevance of SNAP25

• Treatment with botulinum toxin (BoNT) E or with tetanus toxin (TeTx), induced cleavage and inactivation of SNAP-25 and VAMPs, respectively [1].
• Immunohistochemistry showed that non-SCLC tumors were negative for SNAREs and VMATs, with the exception of immunostaining for SNAP-25 and syntaxin1 in 3 of 10 adenocarcinomas [2].
• In a previous paper we have shown reduced amounts of SNAP-25 protein in adult Down Syndrome (DS) brain [3].
• The synaptosomal associated protein of 25kDa (SNAP-25) is widely distributed in the brain and reduced in neurodegenerative diseases [3].
• In this work, neuroblastoma cells expressing synaptotagmin I, a protein shown to be bound by BoNT/A, were used to determine whether specific gangliosides were necessary for BoNT/A activity as measured by synaptosomal-associated protein of 25 kDa (SNAP-25) cleavage [4].

Psychiatry related information on SNAP25

• We measured the level of SNAP-25 in the CSF and symptoms with the Brief Psychiatric Rating Scale (BPRS) [5].
• Decreased levels of synaptosomal associated protein 25 in the brain of patients with Down syndrome and Alzheimer's disease [6].
• The reported changes in SNAP-25 levels appear to be disease specific, separating synaptic pathology in unipolar depression from that observed in schizophrenia and bipolar disorders [7].
• Scores for the seemingly desirable factors of the "Super Person" or "Do Your Own Thing" were negatively correlated with intake of several nutrients; scores on the self-perception of a "Traditional" orientation to life were positively related to calcium intake and meal patterns [8].
• Perceptions of the Jackson-Timberlake Super Bowl incident: role of sexism and erotophobia [9].

High impact information on SNAP25

• Otoferlin binds Ca(2+) and displays Ca(2+)-dependent interactions with the SNARE proteins syntaxin1 and SNAP25 [10].
• Hybridization with the 9q34.3 probe detected multiple transcripts in SUP-T1 RNA and small amounts of larger transcripts in T cells lacking the t(7;9)(q34;q34.3) translocation [11].
• Sequence analysis of DNA from the t(7;9)(q34;q34.3) translocation of SUP-T1 revealed that chromosome 9 DNA had recombined with DNA 5' to rearranged D-J regions in the beta T cell receptor gene of chromosome 7 [11].
• DNA containing breakpoints of two different t(7;9) chromosomal translocations was cloned from the T lymphoblastic tumor cell lines SUP-T1 and SUP-T3 [11].
• We now demonstrate that whereas syntaxin and SNAP-25 in target membranes are freely available for SNARE complex formation, availability of synaptobrevin on synaptic vesicles is very limited [12].

Chemical compound and disease context of SNAP25

• In permeabilized ECL cells, addition of calcium results in histamine release, which can be inhibited by tetanus toxin and botulinum neurotoxin A, underlining the functional importance of the synaptosome-associated protein of 25 kDa (SNAP-25) and synaptobrevin [13].
• By contrast, other amino-acid changes in the same region do not affect CD4 binding but restrict viral tropism: virions containing isoleucine substitutions at position 425 lose their ability to infect a monocyte cell line (U937 cells) but can still infect T-lymphocyte cell lines (CEM, SUP-T1) and activated human peripheral blood lymphocytes [14].
• To investigate the origin of grumose (foamy) spheroid bodies (GFSB), the expression of two proteins associated with axonal regeneration, i.e., phosphotyrosine and 25-kDa synaptosomal-associated protein (SNAP-25), was immunohistochemically assessed in GFSB in the substantia nigra pars reticulate (SNPR) of progressive supranuclear palsy (PSP) [15].
• In the immunohistochemical analysis, decreases in SNAP-25 and synaptophysin immunoreactivities in the strata radiatum and oriens, especially around the apical dendrite of CA1 neurons, and disappearance of SNAP-25 immunoreactivity in the alveus were observed on day 2 after ischemia [16].
• To study the efficacy and safety of Super Malic, a proprietary tablet containing malic acid (200 mg) and magnesium (50 mg), in treatment of primary fibromyalgia syndrome (FM) [17].

Biological context of SNAP25

• These results provide the first direct evidence that rafts regulate SNARE function and exocytosis and identify the central cysteine-rich region of SNAP25/23 as an important regulatory domain [18].
• Synaptosome-associated protein of 25 kDa (SNAP25) is a plasma membrane Q (containing glutamate)-SNARE essential for Ca(2+)-dependent secretory vesicle-plasma membrane fusion in neuroendocrine cells [19].
• Synaptic core complex of synaptobrevin, syntaxin, and SNAP25 forms high affinity alpha-SNAP binding site [20].
• The small-interfering RNA-mediated down-regulation of SNAP25 exerted effects similar to those of BoNT E expression [19].
• However, a substantial intracellular pool of SNAP25 is maintained by endocytosis [19].

Anatomical context of SNAP25

• PC12 cells were engineered that express the light chain of botulinum neurotoxin; in these cells all of the SNAP25 was cleaved to a lower molecular weight form, and regulated exocytosis was essentially absent [18].
• Our results indicate that SNAP25 has a second function as an endosomal Q-SNARE in trafficking from the sorting endosome to the recycling endosome and that BoNT E has effects linked to disruption of the endosome recycling pathway [19].
• Our previous analyses showed that SNARE proteins (syntaxin 1A/SNAP25/VAMP1) are concentrated at both poles of hair cells, consistent with their involvement in membrane delivery at both locations [21].
• Soluble N -ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), including synaptosome-associated proteins of 25 kDa (SNAP25), syntaxins, and vesicle-associated membrane proteins (VAMP), are essential for regulated exocytosis of synaptic vesicles in neurotransmission [22].
• Because Ca(2+) channels in hair cells are poised to interact with synaptic proteins, we also co-expressed the Ca(V)1.3alpha(1) subunit with syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome associated protein of 25 kDa (SNAP25) [23].

Associations of SNAP25 with chemical compounds

• This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate [24].
• In contrast to its behavior in neurons, the distribution of SNAP-25 in MDCK cells remained unaltered by treatment with dibutyryl cAMP or forskolin, which, however, caused an increased growth of the primary cilia [25].
• The amisyn coil domain prevents the SNAP-25 C-terminally mediated rescue of botulinum neurotoxin E inhibition of norepinephrine exocytosis in permeabilized PC12 cells to a greater extent than it prevents the regular exocytosis of these vesicles [26].
• Immunofluorescent localizations reveal peripheral SNAP-25 expression on osteoblastic cells, particularly at intercellular contact sites, colocalizing with immunoreactive glutamate and the synaptic vesicle-specific protein, synapsin I [27].
• RESULTS: In both haloperidol (p =.001) and placebo (p =.001) treatment conditions, SNAP-25 was elevated [5].

Physical interactions of SNAP25

• The sites of interaction, determined from in vivo and in vitro assays, are the N-terminus of SNAP25 (residues 1-84) and the cargo-binding domain of kinesin heavy chain (residues 814-907) [28].
• The mutant SNAP-25 forms were all found to bind syntaxin 1A with equal efficacy [29].
• Using atomic force microscopy we show that the SNARE-like domain of tomosyn-1 can form a complex with syntaxin-1 and SNAP25 but displays binding forces that are weaker than those observed for VAMP2 (237+/-13 versus 279+/-3 pN) [30].
• This reaction leads to the previously described disassembly of the fusion complex, since synaptobrevin binding to syntaxin is also reduced. alpha-SNAP binds to a carboxyl-terminal syntaxin fragment (residues 194-288) that also binds synaptobrevin and SNAP-25 [31].
• Neurosecretion is catalyzed by assembly of a soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE)-complex composed of SNAP-25, synaptobrevin and syntaxin [32].

Regulatory relationships of SNAP25

• This phenotype was not rescued when syntaxin 1A was co-expressed with SNAP-25 [33].
• SNAP-23 is the ubiquitously expressed homologue of the neuronal SNAP-25, which functions in synaptic vesicle fusion [25].
• Here we demonstrate that SNAP-25 efficiently inhibits GAT-1 reuptake function in the presence of syntaxin 1A [34].
• Furthermore, munc13 expressed with syntaxin1A and munc18 promoted redistribution of a cytosolic SNAP25 mutant to the membrane, a result indicative of syntaxin1A-SNAP25 SNARE pairing [35].
• CONCLUSIONS: Super-selective cavernous sinus sampling with hypothalamic stimulating hormone administration can provide accurate localization of the responsible lesion in patients with ACTH-producing pituitary adenoma [36].

Other interactions of SNAP25

• Assembly of a ternary complex by the predicted minimal coiled-coil-forming domains of syntaxin, SNAP-25, and synaptobrevin. A circular dichroism study [37].
• Furthermore, expression of a cytosolic mutant syntaxin 1A did not interfere with SNAP-25 membrane interactions or palmitoylation in the neuronal cell line NG108-15 [33].
• We studied the N-terminal coiled-coil domain of SNAP-23 (SNAP-23N), a non-neuronal homologue of SNAP-25, and its interaction with other coiled-coil domains [38].
• Here, we have designed three peptides, which correspond to sequences located in the syntaxin-1A H3 domain, the C-terminal domain of SNAP-25, and a conserved central domain of synaptobrevin-2, that exhibit a high propensity to form a minimal trimeric coiled-coil [37].
• Our findings continue to support SNAP25 in the susceptibility to ADHD [24].

Analytical, diagnostic and therapeutic context of SNAP25

• GST-pull-down and immunoprecipitation assays showed direct binding of SIP30 to SNAP25 [22].
• Cloning and sequence analysis of the human SNAP25 cDNA [39].
• The presence of SNAP-25 protein in 3T3-L1 cells was demonstrated by immunofluorescence microscopy using an anti-SNAP-25 monoclonal antibody [40].
• Here it is shown, using reverse transcriptase PCR, that messages for both SNAP-25 isoforms are expressed in primary pancreatic B and non-B cells as well as in insulin-secreting cell lines [41].
• The presence of SNAP-25 and syntaxin1 in SCLC was confirmed by RT-PCR performed with material extracted from paraffin sections [2].

References