The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations.

Abstract

Abstract. cDNA clones of a neuronal-specific mRNA encoding a novel 25-kD synaptosomal protein, SNAP-25, that is widely, but differentially expressed by diverse neuronal subpopulations of the mammalian nervous system have been isolated and characterized. The sequence of the SNAP-25 cDNA revealed a single open reading frame that encodes a primary translation product of 206 amino acids. Antisera elicited against a 12-amino acid peptide, corresponding to the carboxyterminal residues of the predicted polypeptide sequence, recognized a single 25-kD protein that is associated with synaptosomal fractions of hippocampal preparations. The SNAP-25 polypeptide remains associated with synaptosomal membrane components after hypoosmotic lysis and is released by nonionic detergent but not high salt extraction. Although the SNAP-25 polypeptide lacks a hydrophobic stretch of residues compatible with a transmembrane region, the amino terminus may form an amphiphilic helix that may facilitate alignment with membranes. The predicted amino acid sequence also includes a cluster of four closely spaced cysteine residues, similar to the metal binding domains of some metalloproteins, suggesting that the SNAP-25 polypeptide may have the potential to coordinately bind metal ions. Consistent with the protein fractionation, light and electron microscopic immunocytochemistry indicated that SNAP-25 is located within the presynaptic terminals of hippocampal mossy fibers and the inner molecular layer of the dentate gyrus. The mRNA was found to be enriched within neurons of the neocortex, hippocampus, piriform cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of the cerebellum. The distribution of the SNAP-25 mRNA and the association of the protein with presynaptic elements suggest that SNAP-25 may play an important role in the synaptic function of specific neuronal systems.

The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

“…[8][9][10][11][12][13][14][15] The synaptosomalassociated protein of 25 kDa (SNAP-25) gene lies in an area of previous suggestive linkage to intelligence (20p12-p11.2), 3 and is highly expressed by neurons in the hippocampus. [16][17][18] The SNAP-25 gene product is a presynaptic plasma membrane protein that is an integral component of the vesicle docking and fusion machinery that regulates neurotransmitter release. 17,19,20 It is also implicated in axonal growth and synaptic plasticity.…”

“…[16][17][18] The SNAP-25 gene product is a presynaptic plasma membrane protein that is an integral component of the vesicle docking and fusion machinery that regulates neurotransmitter release. 17,19,20 It is also implicated in axonal growth and synaptic plasticity. 21 Three lines of evidence suggest a major role of SNAP-25 in learning and memory in humans.…”

“…During development, SNAP-25 is also involved in synaptogenesis, forming presynaptic sites and neuritic outgrowth. 17,21 SNAP-25 is thought to be differentially expressed in the brain, and is primarily present in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular cells. In the mature brain, expression is mainly seen at presynaptic terminals.…”

“…In the mature brain, expression is mainly seen at presynaptic terminals. 17 SNAP-25 exists in two splicing variants in relation to exon 5, SNAP-25a and SNAP-25b. Both isoforms differ in only nine out of 39 amino acids encoded by the alternative spliced exons, 44 resulting in a differentiated membrane anchoring relative to cysteine residues involved in post-transcriptional fatty acylation.…”

SNAP‐25 is present on chromaffin granules and acts as a SNAP receptor

“…NSF is an ATPase and contains two homologous nucleotide-binding regions [3,4], and SNAPs mediate the association of NSF with membranes [5,6]. S611ner et al [7] identified VAMP-2 [8,9], syntaxin 1 [10][11][12], and SNAP-25 [13] as SNAP receptors (SNAREs). NSF, SNAPs and SNAREs are associated to form a 20S complex in membranes, and this complex is disassembled by Mg2+-ATP, whereby NSF is released from the membranes [7,14,15].…”