Disease relevance of SNAP25

• In order to evaluate the role of this layer in different kinetic components of secretion, we used the Semliki Forest virus (SFV) system to infect adrenal chromaffin cells with SNAP-25 Q174L, a point mutant in the zero layer [1].

High impact information on SNAP25

• The alpha-SNAP-SNARE complex can bind NSF, and NSF-dependent hydrolysis of ATP dissociates the complex, separating syntaxin, SNAP-25, and VAMP [2].
• Thus we assign a dual role to SNAP-25 and suggest that its nine C-terminal amino acids are directly involved in coupling the calcium sensor to the final step in exocytosis [3].
• Plasma membrane disruptions are resealed by an active molecular mechanism thought to be composed, in part, of kinesin, CaM kinase, snap-25, and synaptobrevin [4].
• Kinetics of single granule fusions from cells expressing truncated forms showed slow onset and decay times when compared with control cells expressing full SNAP-25 [5].
• Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses [6].

Biological context of SNAP25

• Synthetic peptides patterned after the C-terminus of synaptosomal associated protein of 25 kDa (SNAP25) efficiently abrogate regulated exocytosis [7].
• In contrast, the use of SNAP25 N-terminal-derived peptides to modulate SNAP receptors (SNARE) complex assembly and neurosecretion has not been explored [7].
• We conclude that a small domain of the SNAP-25 C terminus and its counterpart in synaptobrevin play an essential role in the final membrane fusion step of exocytosis [8].
• Point mutations in the C-terminal domain of SNAP-25 (K201E and L203E) produced a marked inhibition of secretion, whereas single (Q174K, Q53K) and double mutants (Q174K/Q53K) of amino acids from the so-called zero layer only produced a moderate alteration in secretion [8].
• Fusion proteins made of green fluorescent protein coupled to SNAP-25 or synaptobrevin were overexpressed in bovine chromaffin cells in order to study the role of critical protein domains in exocytosis [8].

Anatomical context of SNAP25

• In bovine chromaffin cells, syntaxin and SNAP-25 colocalize in defined clusters that average 700 nm in diameter and cover 10% of the plasma membrane [9].
• High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E [9].
• VAMP or synaptobrevin was present both in large dense-core vesicles and in lighter vesicles, whereas SNAP-25, syntaxin, and two types (N and L) of Ca2+ channels were found in a special population of lighter vesicles but were not present in large dense-core vesicles or at the most in very low concentrations [10].
• SNAP-25 is present on chromaffin granules and acts as a SNAP receptor [11].
• SNAP-25, a synaptosomal associated membrane protein of 25 kDa, participates in the presynaptic process of vesicle-plasma membrane fusion that results in neurotransmitter release at central nervous system synapses [12].

Associations of SNAP25 with chemical compounds

• Synaptic vesicle exocytosis requires three SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) proteins: syntaxin and SNAP-25 on the plasma membrane (t-SNAREs) and synaptobrevin/VAMP on the synaptic vesicles (v-SNARE) [13].
• These interesting observations suggest that C1 can only efficiently cleave SNAP-25 in intact cells, possibly due to the existence therein of a unique conformation and/or the participation of accessory factors [14].
• Cleavage of SNAP-25 by BoNT/A also had a larger inhibitory effect on noradrenaline release than on adrenaline release [15].
• Mastoparan, which directly activates G0, selectively inhibited priming and blocked dissociation of the SNAP-25/VAMP-2 complex [16].
• Peptides that mimic the carboxy-terminal domain of SNAP-25 block acetylcholine release at an Aplysia synapse [17].

Physical interactions of SNAP25

• In this study, we examined whether G0 controls such dissociation of the SNAP-25/VAMP-2 complex in the regulation of priming [16].

Regulatory relationships of SNAP25

• Mitogen-activated protein kinase is activated by Ca(2+) entry through L- and N-type channels and regulates Ca(2+)-induced SNAP-25 expression [18].

Other interactions of SNAP25

• Our study reveals that, in the absence of calcium, native synaptotagmin 1 binds the t-SNARE heterodimer, formed from syntaxin and SNAP-25 [13].
• A complex of rab3A, SNAP-25, VAMP/synaptobrevin-2 and syntaxins in brain presynaptic terminals [19].
• Basal expression of SNAP-25 was also modified by the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate, but not by Gö6976, a PKC-alpha inhibitor, suggesting that the Ca(2+)-insensitive PKC-epsilon isoform control basal expression of SNAP-25 in these cells [20].

Analytical, diagnostic and therapeutic context of SNAP25

• High-resolution 2D SDS-PAGE revealed multiple SDS-resistant SNARE complexes having a wide range of sizes and in which SNAP-25 and syntaxin predominate over synaptobrevin [21].
• Using immunoprecipitation, we found that SNAP-25 was present in a complex with syntaxin, synaptobrevin, synaptotagmin, NSF, alpha-SNAP and other unidentified polypeptides [22].
• In line with this result we localized SNAP-25 by immunogold electron microscopy not only to the plasmalemma but also to the chromaffin vesicle membrane [23].
• Prolonged incubation with high K(+) (38 mM) or 1,1-dimethyl-4-phenyl-piperazinium (DMPP), a nicotinic receptor agonist, significantly increased SNAP-25 protein and mRNA expression, as assessed by immunoblotting and semi-quantitative RT-PCR analysis [20].
• Immunocytochemistry confirmed the presence of SNAP-25 in cultured chromaffin cells and showed plasma membrane staining [22].

References