Abstract
Fusion between opposing cellular membranes is essential for numerous cellular activities such as protein maturation, neurotransmission, hormone secretion, and enzyme release. The universal molecular mechanism of membrane fusion involves Ca2+, and the assembly of a specialized set of proteins present in the opposing membrane bilayers. For example in cell secretion, target membrane proteins at the cell plasma membrane SNAP-25 and syntaxin termed t-SNAREs, and secretory vesicle-associated protein VAMP or v-SNARE, are part of the conserved protein complex involved in fusion of opposing membranes. In the presence of Ca2+, t-SNAREs and v-SNARE in opposing bilayers interact and self-assemble in a ring conformation, to form conducting channels. Such self-assembly of t-/v-SNARE ring occurs only when the respective SNAREs are in association with membrane. The size of the SNARE ring complex is dependent on the curvature of the opposing bilayers. Electron density map and 3-D topography of the SNARE ring complex, suggests the formation of a leak-proof channel measuring 25 Å in ring thickness, and 42 Å in height. The mechanism of membrane-directed SNARE ring complex assembly, and the mathematical prediction of SNARE ring size, has been determined. X-ray diffraction measurements and simulation studies have further advanced that membrane-associated t-SNAREs and v-SNARE overcome repulsive forces to bring the opposing membranes close to within a distance of approximately 2.8 Å. Calcium is then able to bridge the closely apposed bilayers, leading to the release of water from hydrated Ca2+ ions as well as the loosely coordinated water at phospholipid head groups, leading to membrane destabilization and fusion.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Malhotra V, Orci L, Glick BS et al (1988) Role of an N-ethylmaleimide-sensitive transport component in promoting fusion of transport vesicles with cisternae of the Golgi stack. Cell 54:221–227
Bennett MK, Calakos N, Scheller RH (1992) Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257:255–259
Oyler GA, Higgins GA, Hart RA et al (1989) The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J Cell Biol 109:3039–3052
Trimble WS, Cowan DM, Scheller RH (1988) VAMP-1: a synaptic vesicle-associated integral membrane protein. Proc Natl Acad Sci USA 85:4538–4542
Cho SJ, Kelly M, Rognlien KT et al (2002) SNAREs in opposing bilayers interact in a circular array to form conducting pores. Biophys J 83:2522–2527
Cho WJ, Jena BP (2007) N-ethylmaleimide-Sensitive Factor is a Right-Handed Molecular Motor. J Biomed Nanotech 3:209–211
Cho WJ, Jeremic A, Jena BP (2005) Size of supramolecular SNARE complex: membrane-directed self-assembly. J Am Chem Soc 127:10156–10157
Jeremic A, Cho WJ, Jena BP (2004) Membrane fusion: what may transpire at the atomic level. J Biol Phys Chem 4:139–142
Jeremic A, Kelly M, Cho JA et al (2004) Calcium drives fusion of SNARE-apposed bilayers. Cell Biol Int 28:19–31
Jeremic A, Quinn AS, Cho WJ et al (2006) Energy-dependent disassembly of self-assembled SNARE complex: observation at nanometer resolution using atomic force microscopy. J Am Chem Soc 128:26–27
Weber T, Zemelman BV, McNew JA et al (1998) SNAREpins: minimal machinery for membrane fusion. Cell 92:759–772
Cho WJ, Lee JS, Ren G et al (2011) Membrane-directed molecular assembly of the neuronal SNARE complex. J Cell Mol Med 15:31–37
Bako I, Hutter J, Palinkas G (2002) Car–Parrinello molecular dynamics simulation of the hydrated calcium ion. J Chem Phys 117:9838–9843
Chialvo AA, Simonson JM (2003) The structure of CaCl2 aqueous solutions over a wide range of concentration. Interpretation of diffraction experiments via molecular simulation. J Chem Phys 119:8052–8061
McIntosh TJ (2000) Short-range interactions between lipid bilayers measured by X-ray diffraction. Curr Opin Struct Biol 10:481–485
Portis A, Newton C, Pangborn W et al (1979) Studies on the mechanism of membrane fusion: evidence for an intermembrane Ca2+-phospholipid complex, synergism with Mg2+, and inhibition by spectrin. Biochemistry 18:780–790
Laroche G, Dufourc EJ, Dufourcq J et al (1991) Structure and dynamics of dimyristoylphosphatidic acid/calcium complexes by 2H NMR, infrared, spectroscopies and small-angle x-ray diffraction. Biochemistry 30:3105–3114
Potoff JJ, Issa Z, Manke CW, Jr et al (2008) Ca2+-dimethylphosphate complex formation: providing insight into Ca2+-mediated local dehydration and membrane fusion in cells. Cell Biol Int 32:361–366
Cook JD, Cho WJ, Stemmler TL et al (2008) Circular dichroism (CD) spectroscopy of the assembly and disassembly of SNAREs: The proteins involved in membrane fusion in cells. Chem Phy Lett 462:6–9
Cohen FS, Niles WD (1993) Reconstituting channels into planar membranes: a conceptual framework and methods for fusing vesicles to planar bilayer phospholipid membranes. Methods Enzymol 220:50–68
Kelly ML, Woodbury DJ (1996) Ion channels from synaptic vesicle membrane fragments reconstituted into lipid bilayers. Biophys J 70:2593–2599
Woodbury DJ (1999) Nystatin/ergosterol method for reconstituting ion channels into planar lipid bilayers. Methods Enzymol 294:319–339
Woodbury DJ, Miller C (1990) Nystatin-induced liposome fusion. A versatile approach to ion channel reconstitution into planar bilayers. Biophys J 58:833–839
Jeong EH, Webster P, Khuong CQ et al (1998) The native membrane fusion machinery in cells. Cell Biol Int 22:657–670
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Jena, B.P. (2011). Role of SNAREs in Membrane Fusion. In: Dittmar, T., Zänker, K.S. (eds) Cell Fusion in Health and Disease. Advances in Experimental Medicine and Biology, vol 713. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0763-4_3
Download citation
DOI: https://doi.org/10.1007/978-94-007-0763-4_3
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-0762-7
Online ISBN: 978-94-007-0763-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)