The SM (Sec1/Munc18-like) protein Munc18-1 and the soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin/VAMP (vesicle-associated membrane protein) constitute the core fusion machinery for synaptic vesicle exocytosis. Strikingly, Munc18-1 interacts with neuronal SNARE proteins in two distinct modes (i.e., with isolat...

BACKGROUND Translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the plasma membrane is responsible for the increased rate of glucose transport into fat and muscle cells in response to insulin. This represents a specialised form of regulated membrane trafficking. Intracellular membrane traffic is subject to multiple levels of regulation by conserved families...

One of the most conspicuous morphological differences of eucaryotic cells from procaryotic cells is the presence of several membrane compartments within the cell. In order to maintain these organelles, eucaryotic cells transfer membrane structural elements, such as proteins and lipids, between the organelles. In this transfer system, small-size membrane vesicles containing structural elements b...

SNAREs (N-ethylmaleimide-sensitive factor adaptor protein receptors) have been often seen to have a dishomogeneous distribution on membranes and are apparently present in excess of the amount required to assure correct vesicle traffic. It was also shown in few cases that SNARE on the target membrane (t-SNARE) with a fusogenic role, can become non-fusogenic when overexpressed. When SNAREs concen...

The SNARE complex, consisting of three proteins (VAMP2, syntaxin, and SNAP-25), is thought to drive membrane fusion by assembling into a four-helix bundle through a zippering process. In support of the above zippering model, a recent single-molecule optical tweezers experiment by Gao et al. revealed a sequential unzipping of SNARE along VAMP2 in the order of the linker domain → the C-terminal d...

The transport of cargo in eukaryotic cells is mediated by the movement of membranous vesicles that pinch off from one membrane and fuse with another. An essential part of this process is the interaction between SNARE (soluble NSF attachment protein receptors) proteins from the vesicle (v-SNARE) and target (t-SNARE) membranes. The resulting SNARE complexes are parallel fourhelix coiled-coil stru...

Although some of the principles of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function are well understood, remarkably little detail is known about sec1/munc18 (SM) protein function and its relationship to SNAREs. Popular models of SM protein function hold that these proteins promote or maintain an open and/or monomeric pool of syntaxin molecules available for SNARE c...

A 63-year-old man presented to our hospital with chronic abdominal pain associated with intermittent periods of postprandial vomiting. Esophagogastroduodenoscopy and endoscopic ultrasound confirmed the diagnosis of a lipoma in the second portion of the duodenum. Owing to the unavailability of a therapeutic gastroscope, a conventional polypectomy snare was modified (▶Fig. 1) in order to be used ...

Genetic and biochemical evidence has established that a SNARE complex consisting of syntaxin 5 (Sed5)-mYkt6 (Ykt6)-GOS28 (Gos1)-GS15 (Sft1) is required for transport of proteins across the Golgi stack in animals (yeast). We have utilized quantitative immunogold labeling to establish the cis-trans distribution of the v-SNARE GS15 and the t-SNARE subunits GOS28 and syntaxin 5. Whereas the distrib...

Pathogens use diverse molecular machines to penetrate host cells and manipulate intracellular vesicular trafficking. Viruses employ glycoproteins, functionally and structurally similar to the SNARE proteins, to induce eukaryotic membrane fusion. Intracellular pathogens, on the other hand, need to block fusion of their infectious phagosomes with various endocytic compartments to escape from the ...