SNARE Proteins - From Membranes to Genomes

Abstract

Abstract:The function and the organization of eukaryotic cells require directional transport of vesicles between compartments. This sort of membrane flow relies on the presence of docking and fusion machinery. The core of this machinery is a protein complex composed of syntaxin, SNAP-25 and VAMP, collectively termed SNAREs. A correct interaction among SNARE prototypes is essential for fruitful docking and fusion. Analysis of large-scale sequencing projects reveals that each of the SNARE proteins (syntaxin, SNAP-25 and VAMP) is a member of a large protein family that is represented in every eukaryotic genome. The diversity among the three SNARE prototypes allows an enriched combinatorial make-up to meet a wide range of cellular demands for secretion.Herein, we discuss the diversity in SNARE proteins from a genomic perspective. We combine information from large-scale sequence data with structural and functional classifications of SNAREs. Using a sequence-based automated protein classification tool, we expose weak but significant connections among all three SNARE protein clusters. These connections define a local evolutionary network within the protein universe. Genomic data allows us to identify classical SNAREs as well as their remote evolutionary relatives. We focus on the SNARE representatives from human and plant genomes to discuss the source of complexity and specificity for docking and fusion in a eukaryotic cell. How many of the potential SNARE combinations are indeed valid in vivo, and to what extent does each combination specify a biochemical and biophysical unique entity, is yet to be experimentally determined. THE SNARE PROTEINS -PAST AND PRESENTThe process of vesicle trafficking and secretion has been investigated in great detail over the last decade (reviewed by [1][2][3][4][5]). Investigators in the field of secretion seem to have come to a consensus that the fusion event relies on a small number of interacting proteins [2,[6][7][8]. The key proteins in this set are syntaxin, SNAP-25, VAMP and variants thereof. These proteins are collectively known as SNAREs [9]. SNARE is an acronym for SNAP receptor, indicating that these proteins function as receptors for NSF (Nethylmaleimide Sensitive Fusion protein) and SNAPs (Soluble NSF Attachment Protein). Association with SNAPs and NSF forms a fusion particle that is essential for vesicular trafficking among subcellular compartments [10,11]. These receptors are localized to two separate membranes that are to be fused [12]. According to their expected localization, they are divided between those on the vesicular membrane (v-SNARE) and those on the target membrane (t-SNARE). The first set of SNAREs identified from solubilized brain extracts includes VAMP/ synaptobrevin on the synaptic vesicle membrane (v-SNARE) and two t-SNAREs, syntaxin and SNAP-25 (from the plasma membrane).Immediately following the identification of mammalian SNAREs, homologues were found in other organisms [13][14][15][16]. It became clear that all three SNARE prototypes are *Address corres...

SNARE‐mediated membrane traffic modulates RhoA‐regulated focal adhesion formation

“…During the process of intracellular membrane trafficking, vesicles are shuttled between the different compartments of a cell. Key proteins involved in vesicular transport are the SNARE (soluble NSF attachment protein receptor, where NSF stands for N ‐ethylmaleimide‐sensitive factor) family of membrane proteins [13–15]. SNAREs are small transmembrane proteins that can be roughly classified into two broad categories: vesicle‐SNARES (v‐SNAREs, found on vesicles) and target‐SNAREs (t‐SNAREs, found on target compartments) [14,16].…”

“…Key proteins involved in vesicular transport are the SNARE (soluble NSF attachment protein receptor, where NSF stands for N ‐ethylmaleimide‐sensitive factor) family of membrane proteins [13–15]. SNAREs are small transmembrane proteins that can be roughly classified into two broad categories: vesicle‐SNARES (v‐SNAREs, found on vesicles) and target‐SNAREs (t‐SNAREs, found on target compartments) [14,16]. The main function of SNAREs is to form cytoplasmic coiled‐coil bundles to bridge vesicle and target membranes as they fuse [17–19].…”

SNAREs: Cogs and Coordinators in Signaling and Development

“…At the nerve synapse, t-SNAREs contribute three a-helices, one from syntaxin (Qa) and two from the N-terminal (Qb) and C-terminal (Qc) halves of SNAP-25. Intriguingly, the tripartite assembly of the neuronal SNARE complex is far less common by comparison with the model characterized by a single SNARE coil per polypeptide (Linial, 2001). The latter appears to be the norm also for plants.…”

Setting SNAREs in a Different Wood

“…This tripartite assembly of the SNARE complex is far less common outside the neuronal model. Indeed, the norm is generally characterized by a single SNARE coil per polypeptide (18, 19), even among mammals (20). This situation is certainly the case for the model plant Arabidopsis that includes 18 syntaxin‐like Qa‐SNAREs, 18 Qb‐ and Qc‐SNAREs, but only three SNAP‐25‐like (Qb + Qc)‐SNAREs, and for rice that includes 14 Qa‐SNAREs, 26 Qb‐ and Qc‐SNAREs and, again, only three SNAP25‐like (Qb + Qc)‐SNAREs [(1) see also Table 1].…”

“…The rice genome, unlike that of Arabidopsis , harbours a single gene encoding an α‐SNAP‐like protein, but like Arabidopsis , it includes one NSF‐like ATPase, a number of CDC48‐like ATPases and three Sec1‐like peripheral binding proteins that in mammals, yeast and Drosophila regulate syntaxin accessibility and SNARE interactions (3, 36). Like Arabidopsis , a brief scan of the rice‐encoded genes shows overlaps with mammals associated with the syntaxin‐like Qa‐SNAREs and additional blending with patterns more typical of yeast (1, 19). Elements paralleling the yeast trans ‐Golgi network (TGN)‐to‐vacuole pathways are evident, notably genes encoding three Vti‐like proteins in rice and four in Arabidopsis , the latter including AtVti11 (=AtVti1a) and AtVti12 (=AtVTI1b) that associate with (pre‐) vacuolar markers AtSyp21, AtSyp51 and AtSyp61 (37, 38).…”