scholarly journals An Elaborate Classification of SNARE Proteins Sheds Light on the Conservation of the Eukaryotic Endomembrane System

2007 ◽  
Vol 18 (9) ◽  
pp. 3463-3471 ◽  
Author(s):  
Tobias H. Kloepper ◽  
C. Nickias Kienle ◽  
Dirk Fasshauer
Keyword(s):  
Sequence Divergence ◽  
Eukaryotic Cell ◽  
Snare Proteins ◽  
Endomembrane System ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Transport Vesicles ◽  
Sensitive Factor ◽  
Receptor Family

Proteins of the SNARE (soluble N-ethylmalemide–sensitive factor attachment protein receptor) family are essential for the fusion of transport vesicles with an acceptor membrane. Despite considerable sequence divergence, their mechanism of action is conserved: heterologous sets assemble into membrane-bridging SNARE complexes, in effect driving membrane fusion. Within the cell, distinct functional SNARE units are involved in different trafficking steps. These functional units are conserved across species and probably reflect the conservation of the particular transport step. Here, we have systematically analyzed SNARE sequences from 145 different species and have established a highly accurate classification for all SNARE proteins. Principally, all SNAREs split into four basic types, reflecting their position in the four-helix bundle complex. Among these four basic types, we established 20 SNARE subclasses that probably represent the original repertoire of a eukaryotic cenancestor. This repertoire has been modulated independently in different lines of organisms. Our data are in line with the notion that the ur-eukaryotic cell was already equipped with the various compartments found in contemporary cells. Possibly, the development of these compartments is closely intertwined with episodes of duplication and divergence of a prototypic SNARE unit.

scholarly journals SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events

2017 ◽  
Vol 45 (6) ◽  
pp. 1271-1277 ◽  
Author(s):  
Kamilla M.E. Laidlaw ◽  
Rachel Livingstone ◽  
Mohammed Al-Tobi ◽  
Nia J. Bryant ◽  
Gwyn W. Gould
Keyword(s):  
Membrane Fusion ◽  
Molecular Mechanisms ◽  
Membrane Receptors ◽  
Multivesicular Bodies ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Plasma Membrane Receptors ◽  
Regulated Trafficking ◽  
Receptor Family

Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. We will describe how these proteins are controlled in a range of regulated trafficking events, with particular emphasis on the insulin-stimulated delivery of glucose transporters to the surface of adipose and muscle cells. Here, we focus on a few examples of SNARE phosphorylation which exemplify distinct ways in which SNARE machinery phosphorylation may regulate membrane fusion.

Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis

2012 ◽  
Vol 92 (4) ◽  
pp. 1915-1964 ◽  
Author(s):  
Haruo Kasai ◽  
Noriko Takahashi ◽  
Hiroshi Tokumaru
Keyword(s):  
Membrane Trafficking ◽  
Synaptic Vesicles ◽  
Cell Types ◽  
Snare Proteins ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Large Dense Core Vesicles ◽  
Sensitive Factor ◽  
The Common ◽  
Kinetics Of

The dynamics of exocytosis are diverse and have been optimized for the functions of synapses and a wide variety of cell types. For example, the kinetics of exocytosis varies by more than five orders of magnitude between ultrafast exocytosis in synaptic vesicles and slow exocytosis in large dense-core vesicles. However, in all cases, exocytosis is mediated by the same fundamental mechanism, i.e., the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is often assumed that vesicles need to be docked at the plasma membrane and SNARE proteins must be preassembled before exocytosis is triggered. However, this model cannot account for the dynamics of exocytosis recently reported in synapses and other cells. For example, vesicles undergo exocytosis without prestimulus docking during tonic exocytosis of synaptic vesicles in the active zone. In addition, epithelial and hematopoietic cells utilize cAMP and kinases to trigger slow exocytosis of nondocked vesicles. In this review, we summarize the manner in which the diversity of exocytosis reflects the initial configurations of SNARE assembly, including trans-SNARE, binary-SNARE, unitary-SNARE, and cis-SNARE configurations. The initial SNARE configurations depend on the particular SNARE subtype (syntaxin, SNAP25, or VAMP), priming proteins (Munc18, Munc13, CAPS, complexin, or snapin), triggering proteins (synaptotagmins, Doc2, and various protein kinases), and the submembraneous cytomatrix, and they are the key to determining the kinetics of subsequent exocytosis. These distinct initial configurations will help us clarify the common SNARE assembly processes underlying exocytosis and membrane trafficking in eukaryotic cells.

scholarly journals Endosomal and Phagosomal SNAREs

2018 ◽  
Vol 98 (3) ◽  
pp. 1465-1492 ◽  
Author(s):  
Ilse Dingjan ◽  
Peter T. A. Linders ◽  
Danielle R. J. Verboogen ◽  
Natalia H. Revelo ◽  
Martin ter Beest ◽  
...  
Keyword(s):  
Intracellular Transport ◽  
Snare Proteins ◽  
Intracellular Pathogens ◽  
Snare Protein ◽  
Attachment Protein ◽  
System A ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Organelle Communication ◽  
Factor Attachment Protein Receptor

The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking. Of the 38 SNAREs present in humans, 30 have been identified at endosomes and/or phagosomes. Many of these SNAREs are targeted by viruses and intracellular pathogens, which thereby reroute intracellular transport for gaining access to nutrients, preventing their degradation, and avoiding their detection by the immune system. A fascinating picture is emerging of a complex transport network with multiple SNAREs being involved in consecutive trafficking routes.

scholarly journals Localization, Dynamics, and Protein Interactions Reveal Distinct Roles for ER and Golgi SNAREs

1998 ◽  
Vol 141 (7) ◽  
pp. 1489-1502 ◽  
Author(s):  
Jesse C. Hay ◽  
Judith Klumperman ◽  
Viola Oorschot ◽  
Martin Steegmaier ◽  
Christin S. Kuo ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Protein Interactions ◽  
The Other ◽  
Snare Proteins ◽  
Attachment Protein ◽  
Golgi Transport ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Coated Membranes ◽  
Factor Attachment Protein Receptor

ER-to-Golgi transport, and perhaps intraGolgi transport involves a set of interacting soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins including syntaxin 5, GOS-28, membrin, rsec22b, and rbet1. By immunoelectron microscopy we find that rsec22b and rbet1 are enriched in COPII-coated vesicles that bud from the ER and presumably fuse with nearby vesicular tubular clusters (VTCs). However, all of the SNAREs were found on both COPII- and COPI-coated membranes, indicating that similar SNARE machinery directs both vesicle pathways. rsec22b and rbet1 do not appear beyond the first Golgi cisterna, whereas syntaxin 5 and membrin penetrate deeply into the Golgi stacks. Temperature shifts reveal that membrin, rsec22b, rbet1, and syntaxin 5 are present together on membranes that rapidly recycle between peripheral and Golgi-centric locations. GOS-28, on the other hand, maintains a fixed localization in the Golgi. By immunoprecipitation analysis, syntaxin 5 exists in at least two major subcomplexes: one containing syntaxin 5 (34-kD isoform) and GOS-28, and another containing syntaxin 5 (41- and 34-kD isoforms), membrin, rsec22b, and rbet1. Both subcomplexes appear to involve direct interactions of each SNARE with syntaxin 5. Our results indicate a central role for complexes among rbet1, rsec22b, membrin, and syntaxin 5 (34 and 41 kD) at two membrane fusion interfaces: the fusion of ER-derived vesicles with VTCs, and the assembly of VTCs to form cis-Golgi elements. The 34-kD syntaxin 5 isoform, membrin, and GOS-28 may function in intraGolgi transport.

scholarly journals HOPS drives vacuole fusion by binding the vacuolar SNARE complex and the Vam7 PX domain via two distinct sites

2011 ◽  
Vol 22 (14) ◽  
pp. 2601-2611 ◽  
Author(s):  
Lukas Krämer ◽  
Christian Ungermann
Keyword(s):  
Membrane Fusion ◽  
Snare Complex ◽  
Endomembrane System ◽  
Attachment Protein ◽  
Vacuole Fusion ◽  
Px Domain ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Membrane Tethering

Membrane fusion within the endomembrane system follows a defined order of events: membrane tethering, mediated by Rabs and tethers, assembly of soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) complexes, and lipid bilayer mixing. Here we present evidence that the vacuolar HOPS tethering complex controls fusion through specific interactions with the vacuolar SNARE complex (consisting of Vam3, Vam7, Vti1, and Nyv1) and the N-terminal domains of Vam7 and Vam3. We show that homotypic fusion and protein sorting (HOPS) binds Vam7 via its subunits Vps16 and Vps18. In addition, we observed that Vps16, Vps18, and the Sec1/Munc18 protein Vps33, which is also part of the HOPS complex, bind to the Q-SNARE complex. In agreement with this observation, HOPS-stimulated fusion was inhibited if HOPS was preincubated with the minimal Q-SNARE complex. Importantly, artificial targeting of Vam7 without its PX domain to membranes rescued vacuole morphology in vivo, but resulted in a cytokinesis defect if the N-terminal domain of Vam3 was also removed. Our data thus support a model of HOPS-controlled membrane fusion by recognizing different elements of the SNARE complex.

scholarly journals Sec1/Munc18 protein Vps33 binds to SNARE domains and the quaternary SNARE complex

2012 ◽  
Vol 23 (23) ◽  
pp. 4611-4622 ◽  
Author(s):  
Braden T. Lobingier ◽  
Alexey J. Merz
Keyword(s):  
Protein Function ◽  
Snare Complex ◽  
Snare Proteins ◽  
Missense Mutations ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Biochemical Studies ◽  
Sensitive Factor ◽  
Sm Protein ◽  
Endocytic Traffic

Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins catalyze membrane fusion events in the secretory and endolysosomal systems, and all SNARE-mediated fusion processes require cofactors of the Sec1/Munc18 (SM) family. Vps33 is an SM protein and subunit of the Vps-C complexes HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering), which are central regulators of endocytic traffic. Here we present biochemical studies of interactions between Saccharomyces cerevisiae vacuolar SNAREs and the HOPS holocomplex or Vps33 alone. HOPS binds the N-terminal Habc domain of the Qa-family SNARE Vam3, but Vps33 is not required for this interaction. Instead, Vps33 binds the SNARE domains of Vam3, Vam7, and Nyv1. Vps33 directly binds vacuolar quaternary SNARE complexes, and the affinity of Vps33 for SNARE complexes is greater than for individual SNAREs. Through targeted mutational analyses, we identify missense mutations of Vps33 that produce a novel set of defects, including cargo missorting and the loss of Vps33-HOPS association. Together these data suggest a working model for membrane docking: HOPS associates with N-terminal domains of Vam3 and Vam7 through Vps33-independent interactions, which are followed by binding of Vps33, the HOPS SM protein, to SNARE domains and finally to the quaternary SNARE complex. Our results also strengthen the hypothesis that SNARE complex binding is a core attribute of SM protein function.

scholarly journals Prototypic SNARE proteins are encoded in the genomes of Heimdallarchaeota, potentially bridging the gap between the prokaryotes and eukaryotes

2019 ◽  
Author(s):  
Emilie Neveu ◽  
Dany Khalifeh ◽  
Nicolas Salamin ◽  
Dirk Fasshauer
Keyword(s):  
Gene Transfer ◽  
Eukaryotic Cell ◽  
Snare Proteins ◽  
Eukaryotic Cells ◽  
Endomembrane System ◽  
Intracellular Space ◽  
Sensitive Factor ◽  
Genes Encoding ◽  
Membrane Bound ◽  
Material Exchange

AbstractA defining feature of eukaryotic cells is the presence of numerous membrane-bound organelles that subdivide the intracellular space into distinct compartments. How the eukaryotic cell acquired its internal complexity is still poorly understood. Material exchange among most organelles occurs via vesicles that bud off from a source and specifically fuse with a target compartment. Central players in the vesicle fusion process are the Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor (SNARE) proteins. These small tail-anchored (TA) membrane proteins zipper into elongated four-helix bundles that pull membranes together1–3. SNARE proteins are highly conserved among eukaryotes but are thought to be absent in prokaryotes. Here, we identified SNARE-like factors in the genomes of uncultured organisms of Asgard archaea of the Heimdallarchaeota clade4,5, which are thought to be the closest living relatives of eukaryotes. Biochemical experiments show that the archaeal SNARE-like proteins can interact with eukaryotic SNARE proteins. We did not detect SNAREs in α-proteobacteria, the closest relatives of mitochondria, but identified several genes encoding for SNARE proteins in γ-proteobacteria of the order Legionellales, pathogens that live inside eukaryotic cells. Very probably, their SNAREs stem from lateral gene transfer from eukaryotes. Together, this suggests that the diverse set of eukaryotic SNAREs evolved from an archaeal precursor. However, whether Heimdallarchaeota actually have a simplified endomembrane system will only be seen when we succeed studying these organisms under the microscope.

scholarly journals Identification of Functionally Interacting SNAREs by Using Complementary Substitutions in the Conserved `0' Layer

2005 ◽  
Vol 16 (5) ◽  
pp. 2263-2274 ◽  
Author(s):  
Carmen T. Graf ◽  
Dietmar Riedel ◽  
Hans Dieter Schmitt ◽  
Reinhard Jahn
Keyword(s):  
Snare Complex ◽  
Growth Defect ◽  
Temperature Sensitive ◽  
Central Layer ◽  
Attachment Protein ◽  
Growth Defects ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Factor Attachment Protein Receptor

Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes form bundles of four parallel α-helices. The central `0' layer of interacting amino acid side chains is highly conserved and contains one arginine and three glutamines, leading to the classification of SNAREs into R, Qa, Qb, and Qc-SNAREs. Replacing one of the glutamines with arginine in the yeast exocytotic SNARE complex is either lethal or causes a conditional growth defect that is compensated by replacing the R-SNARE arginine with glutamine. Using the yeast SNARE complex mediating traffic from the endoplasmic reticulum to the Golgi apparatus, we now show that functionally interacting SNAREs can be mapped by systematically exchanging glutamines and arginines in the `0' layer. The Q→ R replacement in the Qb-SNARE Bos1p has the strongest effect and can be alleviated by an Q→ R replacement in the R-SNARE Sec22p. Four Q residues in the central layer caused growth defects above 30°C that were rescued by Q→ R substitutions in the Qa and Qc SNAREs Sed5p and Bet1p, respectively. The sec22(Q)/sed5(R) mutant is temperature sensitive and is rescued by a compensating R→ Q replacement in the R-SNARE Ykt6p. This rescue is attributed to the involvement of Sed5p and Ykt6p in a different SNARE complex that functions in intra-Golgi trafficking.

scholarly journals HOPS Initiates Vacuole Docking by Tethering Membranes before trans-SNARE Complex Assembly

2010 ◽  
Vol 21 (13) ◽  
pp. 2297-2305 ◽  
Author(s):  
Christopher M. Hickey ◽  
William Wickner
Keyword(s):  
Complex Formation ◽  
Present Model ◽  
Snare Complex ◽  
Snare Proteins ◽  
Membrane Association ◽  
Attachment Protein ◽  
Protein Receptor ◽  
Sensitive Factor ◽  
Rab Effector ◽  
Snare Complex Formation

Vacuole homotypic fusion has been reconstituted with all purified components: vacuolar lipids, four soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Sec17p, Sec18p, the Rab Ypt7p, and the hexameric homotypic fusion and vacuole protein sorting complex (HOPS). HOPS is a Rab-effector with direct affinity for SNAREs (presumably via its Sec1-Munc18 homologous subunit Vps33p) and for certain vacuolar lipids. Each of these pure vacuolar proteins was required for optimal proteoliposome clustering, raising the question of which was most directly involved. We now present model subreactions of clustering and fusion that reveal that HOPS is the direct agent of tethering. The Rab and vacuole lipids contribute to tethering by supporting the membrane association of HOPS. HOPS indirectly facilitates trans-SNARE complex formation by tethering membranes, because the synthetic liposome tethering factor polyethylene glycol can also stimulate trans-SNARE complex formation and fusion. SNAREs further stabilize the associations of HOPS-tethered membranes. HOPS then protects newly formed trans-SNARE complexes from disassembly by Sec17p/Sec18p.

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