The proteins NSF and SNAPs are known to participate in several intracellular fusion events, but their exact functions in the fusion process are unclear. Molecular studies have now shown that the ability of NSF to hydrolyse ATP is essential for membrane fusion and that this activity is regulated by SNAPs. This article reviews recent work on NSF and SNAPs, and speculates about how they interact with each other and SNARES to promote membrane fusion.
|Number of pages||5|
|Journal||Trends in Cell Biology|
|State||Published - Feb 1995|
Bibliographical noteFunding Information:
nonhydrolysable ATPyS or with EDTA)s. When excess ATP-Mgzl is added to the formed particle, it disassembles into separate component@. Dis-assembly most likely reflects the structural changes in the ZOS particle that are required to consumate the fusion event, although this has not been demonstrated. In one model for membrane fusion (Fig. 3a), the energy from ATP hydrolysis is used to bring the two membranes together in a way that deforms the target membrane by ‘pulling’ it to the vesicle membrane. By locally deforming the target membrane, tension is generated that could promote bilayer fusions6; this would result in both target and vesicle membranes having increased surface tension. In this simplistic model, the SNARESw ould provide the anchors to each membrane, the SNAPSw ould attach KSF to the SNARES, and NSF would provide the energy needed to gener-ate membrane tension. Once fusion occurred, the dissociated SNARES would be in the same bilayer where they would be unable to interact or to provide a binding site for the SNAPS;t hus, the particle would be disassembled and the process inactivated. In another model (Fig. 3b), membranes would be brought together by the docking complex composed of the V-SNARE and the two t-SNAREs to form a small fusion pore. The 20s fusion particle would form part of a scaffold that surrounds the fusion pore36. In this case, the SNARES would provide the membrane anchors and generate the tension for fusion pore for-mation. Once bound together, the SNARES would form a stable complex restraining the fusion pore such that its open and closed states were in equilib-rium. This state would be consistent with the electro-chemical event known as ‘flickering’37. SNAPS and NSF could then bind to this complex and use the energy from ATP hydrolysis to disrupt the scaffold, thereby releasing the restraint and irreversibly shifting Acknow’ed~ementths e equilibrium. If the pore were closed at the time We thank Thomas of scaffold release, the vesicle could repeat the dock-Sbllner for his ing process and, in a sense, try again. If the pore were helpful discussions, open, it would expand to complete vesicle fusion. Gary Tanigawa for By themselves, neither fusion scenario can com-sequence pletely explain all the data on membrane fusion. As comparisons, more becomes known about the molecular com-susanB uhrow for ponents of the fusion machine more sophisticated ccmment~ on the models will be created and tested. To create these manuscript, and models, it will be important to establish the exact Alan Morgan and stoichiometry of the ZOS particle as well as the ge-Robert D. Burgoyne ometry of the interactions. It will also be essential to for sharing determine the amounts of ATP required for fusion, unpublished data. but this may require the development of an in vitro Our work is fusion assay. With this type of technological advance supported by The we should approach a more detailed molecular University of understanding of intracellular fusion events. Kentucky Research Fund, the American References Cancer Society 1 ROTHMAN, 1. E. (1994) Nature 372, 5543 (S. W. W.), the 2 PRYER, N. K., WUESTEHUBE, L. J. and SCHEKMAN, R. (1992) Howard Hughes Annu. Rev. Biochem. 61,471-516 Medical institute 3 SbLLNER, T. et al. (1993) Nature 362, 31 S-324 and by an NIH 4 SBLLNER, T., BENNETr, M. K., WHITEHEART, 5. W., grant to Patrick 0. SCHELLER, R. H. and ROTHMAN, J. E. (1993) Ceil 75, Brown (E. W. K.). 409-418
ASJC Scopus subject areas
- Cell Biology