Membrane fusion promotion

HSV-1 vims entry is mediated by multiple glycoproteins present in the envelope and is a rather complex process. Initial adhesion to the cellular membrane is mediated by the interaction of gC and gB with glycosaminoglycan heparan sulfate. Subsequently, gD binds to a specific cellular receptor, either a member of the TNF receptor family [herpes vims entry mediator A (HveA)], immunoglobulin superfamily (HveB, HveC), or 3-O-sulfated heparan sulfate. Then, the vims enters the cell through membrane fusion promoted by the gH/gL complex and gB (117). 

Previous studies indicate that osmotic gradients promote membrane fusion, while hyperosmotic conditions inhibit membrane fusion during exocytosis. Consistent with this idea is the observation that the release of lysosomal enzymes from rabbit neutrophils, induced by the chemotactic peptide J -formylmethionyl-leucyl-phenylalanine (FMLP), is inhibited almost 80% in a 700-mosmol/kg medium. Inhibition is immediate (within 10 s), increases with osmolality, and is independent of the osmoticant. Neutrophils loaded with the calcium indicator indo-1 exhibit an FMLP-induced calcium signal that is inhibited by hyperosmolality. Hyperosmolality (700 mosmol/kg) increases basal calcium levels and reduces the peak of the calcium signal elicited by FMLP at concentrations ranging from 10 ° to 10 M. 

Other DUBs have been found to associate with membranes and regulate membrane-associated cellular processes, although they appear not to be membrane anchored like UBP16. The ability of DOA4 to remove ubiquitin from membrane-bound endocytic substrates promotes their degradation in the vacuole or lysosome [71]. DUBs are also important for membrane fusion events as shown by the fact that an OTU domain DUB, VCIP135 (VCP/p47 complex-interacting protein of... 

Peng R, Gadwitz D (2002) Slyl protein bound to Golgi syntaxin Sed5p adows assembly and contributes to specificity of SNARE fusion complexes. J Ced Biol 157 645-55 Pobbati AV, Stein A, Fasshauer D (2006) N- to C-terminal SNARE complex assembly promotes rapid membrane fusion. Science 313 673-6... 

Martens S, Kozlov MM, McMahon HT. How synaptotagmin promotes membrane fusion. Science 2007 316 1205-1208. 

Talbot WA, Zheng L, Lentz BR. Acyl chain unsaturation and vesicle curvature alter outer leaflet packing and promote poly(ehtylene glycol)-mediated membrane fusion. Biochemistry 1997 36 5827-5836. 

One criterion for a bona fide membrane-fusion protein is that membrane fusion can be reconstituted by transfection of the candidate fusion protein into nonfusing cells or by reconstitution into lipid vesicles (White, 1990 White, 1992 White and Blobel, 1989). Transfection of meltrin a into fibroblasts did not lead to an increase in cell fusion (Yagami-Hiromasa et al., 1995). Clearly, failure to reconstitute fusion does not rule out a role in fusion because the cellular fusion machinery may be more complex than viral fusion proteins. Muscle cells might contain other proteins that are required for meltrin a to promote membrane fusion but that are not expressed or active in fibroblasts. Ultimately, the identity of a bona fide cell-cell fusion protein or protein machine will only be determined by reconstituting membrane fusion with defined components. In the interim, it will be important to more accurately understand the roles of meltrin a and fertilin in the cascade of steps that result in membrane fusion and thereby perhaps distinguish between a direct and indirect role in fusion. 

Many studies show that divalent cations promote membrane fusion (27, 28, 29) and thereby may initiate attachment of granules to the insides of plasma membranes during secretion. Actually these ideas (i.e. enzyme activation and fusion of lipoid membranes by calcium), are not mutually exclusive since it is possible that calcium initiates more than one intracellular change to trigger the secretory process. 

Inside the endosome the pH (5.0-6.2) is more acidic and poses the problem of nucleic acid degradation. In the case of viral vectors, their inherent property to undergo conformational changes in the coat proteins promotes endosomal membrane fusion, which helps in protecting them from the endosomal environment, but in the case of nonviral vectors, lysosomotropic agents like chloroquine, membrane-destabilizing peptides such as synthetic N-terminal peptides of rhinovirus VP-1 or influenza virus HA-2 are attached to the cationic complex to mediate endosomal release. 

Within 1-3 years after the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immune deficiency syndrome (AIDS) (1,2), the CD4 molecule was identified as the primary HIV receptor (3). HIV was shown to enter target cells by an initial binding event between the envelope glycoprotein (Env) molecules on the viral membrane and CD4 molecules on the target cell surface, followed by direct, pH-independent membrane fusion. Yet as early as 1986, it became clear that the Env-CD4 interaction was not sufficient to promote the fusion reaction (4-6) several lines of evidence indicated that the target cell must contain an additional human-specific cofactor (7-11), presumably a coreceptor. ... 

To study whether these HL vectors were affecting transfection activity through pH-sensitive changes in membrane fusion within the endosome to promote escape, Chaudhuri et al. used a fluorescence resonance energy transfer (FRET) technique. HL-l/Chol liposomes were incubated with Rhodamine Red -containing liposomes and subjected to... 

If this is a correct interpretation of the labelling changes the key event could be the production of diacylglycerol in the vesicle membrane, if not the plasma membrane as well. Production of this lipid can lead to membrane fusion processes in the erythrocyte membrane (Allan et al., 1976). We suggest therefore that production of diacylglycerol in the synaptosome promotes the membrane fusion required for exocytosis and transmitter release. 

---