241:
192:
228:, it has been postulated that energy released during the assembly process serves as a means for overcoming the repulsive forces between the membranes. There are several models that propose explanation of a subsequent step – the formation of stalk and fusion pore, but the exact nature of these processes remains debated. Two of the most prominent models on
258:
and they would have a substantially more difficult time producing effects such as the "kiss-and-run" when compared with their protein-lined counterparts. Lipid-lined pores effectiveness would also be highly dependent on the composition of both membranes, and its success or failure could vary wildly with changes in elasticity and rigidity.
278:
forming the pore in the cell membrane. As the initial pore expands it incorporates lipids from both bilayers, eventually resulting in complete fusion of the two membranes. The SNARE complex has a much more active role in the protein-lined pore theory; because the pore consists initially entirely of
282:
A protein-lined pore perfectly meets all the observed requirements of the early fusion pore, and while some data does support this theory, sufficient data does not exist to pronounce it the primary method of fusion. A protein-lined pore requires at least five copies of the SNARE complex while fusion
253:
complex, membrane fusion occurs spontaneously. It has been shown that when the two membranes are brought within a critical distance, it is possible for hydrophilic lipid headgroups of one membrane to merge with the opposing membrane. In the lipid-lined fusion pore model, the SNARE complex acts as a
165:
fusion, the vesicle must be within a few nanometers of the target membrane for the fusion process to begin. This closeness allows the cell membrane and the vesicle to exchange lipids which is mediated by certain proteins which remove water that comes between the forming junction. Once the vesicle
257:
While a lipid-lined pore is possible and can achieve all the same properties observed in early pore formation, sufficient data does not exist to prove it is the sole method of formation. There is not currently a proposed mechanism on inter-cellular regulation for fluctuation of lipid-lined pores,
216:
within the SNARE complex and its interaction with the molecule synaptotagmin. Known as the "clamp" hypothesis, the presence of complexin normally inhibits the fusion of the vesicle to the cell membrane. However, binding of calcium ions to synaptotagmin triggers the complexin to be released or
220:
According to the "zipper" hypothesis, the complex assembly starts at the N-terminal parts of SNARE motifs and proceeds towards the C-termini that anchor interacting proteins in membranes. Formation of the "trans"-SNARE complex proceeds through an intermediate complex composed of SNAP-25 and
204:
of membranes belonging to cell and secretory granule, bringing them in proximity and inducing their fusion. The influx of calcium into the cell triggers the completion of the assembly reaction, which is mediated by an interaction between the putative calcium sensor,
244:
In the lipid-lined pore theory both membranes curve toward each other to form the early fusion pore. When the two membranes are brought to a "critical" distance, the lipid head-groups from one membrane insert into the other, creating the basis for the fusion
331:
There is some indication that vesicles may only form a small pore in the presynaptic membrane allowing contents to be released by standard diffusion for a short while before retreating back into the presynaptic cell. This mechanism may be a way around
195:
Molecular machinery driving exocytosis in neuromediator release. The core SNARE complex is formed by four α-helices contributed by synaptobrevin, syntaxin and SNAP-25, synaptotagmin serves as a calcium sensor and regulates intimately the SNARE
254:
scaffold, pulling on the membrane, causing both membranes to pucker so they may reach the critical fusion distance. As the two membranes begin to fuse, a lipid-lined stalk is produced, expanding radially outward as fusion proceeds.
340:
to refill, though it is not thoroughly understood by which mechanism it would refill. This does not exclude full vesicle fusion, but only states that both mechanisms may operate in synaptic clefts.
249:
One possible model for fusion pore formation is the lipid-line pore theory. In this model, once the membranes have been brought into sufficiently close proximity via the "zipper" mechanism of the
140:
or a mixture have been studied by physical chemists. Cardiolipin is found mainly in mitochondrial membranes, and calcium ions play an important role in the respiratory processes mediated by the
286:
In both theories the function of the SNARE complex remains largely unchanged, and the entire SNARE complex is necessary to initiate fusion. It has, however, been proven that
547:
Pigino, Gustavo; Morfini, Gerardo; Brady, Scott (2006). "Chapter 9: Intracellular
Trafficking". In Siegal, George J.; Albers, R. Wayne; Brady, Scott T.; et al. (eds.).
590:
Georgiev, Danko D .; James F . Glazebrook (2007). "Subneuronal processing of information by solitary waves and stochastic processes". In
Lyshevski, Sergey Edward (ed.).
324:
always occurs in vesicle reforming after release of the neurotransmitter. Another proposed mechanism for release of vesicle contents into extracellular fluid is called
296:
is sufficient to drive spontaneous calcium independent fusion of synaptic vesicles containing v-SNAREs. This suggests that in Ca-dependent neuronal exocytosis
914:
316:, some neurochemists have suggested that vesicles occasionally may not completely fuse with presynaptic membranes in neurotransmitter release into the
221:
syntaxin-1, which later accommodates synaptobrevin-2 (the quoted syntaxin and synaptobrevin isotypes participate in neuronal neuromediator release).
144:. The forces involved have been postulated to explain this process in terms of nucleation for agglomeration of smaller supramolecular entities or
279:
SNARE proteins, the pore is easily able to undergo intercellular regulation, making fluctuation and "kiss-and-run" mechanisms easily attainable.
492:"Membrane Fusion and the Lamellar-to-Inverted-Hexagonal Phase Transition in Cardiolipin Vesicle Systems Induced by Divalent Cations"
43:
occurs when secretory vesicles transiently dock and fuse at the base of cup-shaped structures at the cell plasma membrane called
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431:
406:
634:
Kümmel, D.; Krishnakumar, S. S.; Radoff, D. T.; Li, F.; Giraudo, C. G.; Pincet, F.; Rothman, J. E.; Reinisch, K. M. (2011).
343:"Kiss and run" has been shown to occur in endocrine cells, though it has not been directly witnessed in synaptic gaps.
266:
Another possible model for fusion pore formation is the protein-lined pore theory. In this model, after activation of
75:
118:
953:
108:
698:
Jackson, Meyer B.; Chapman, Edwin R. (2006). "Fusion Pores and Fusion
Machines in Ca2+-Triggered Exocytosis".
684:
333:
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is a dual regulator, in absence of Ca ions to inhibit SNARE dynamics, while in presence of Ca ions to act as
113:
856:
Chang, Che-Wei; Hui, Enfu; Bai, Jihong; Bruns, Dieter; Chapman, Edwin R.; Jackson, Meyer B. (2015-04-08).
90:
915:"The t-SNARE syntaxin is sufficient for spontaneous fusion of synaptic vesivles to planar membranes"
858:"A Structural Role for the Synaptobrevin 2 Transmembrane Domain in Dense-Core Vesicle Fusion Pores"
734:
177:
SNARE proteins are also thought to help mediate which membrane is the target of which vesicle.
122:
447:
Papahadjopoulos, Demetrios (1990). "Molecular mechanisms of calcium-induced membrane fusion".
992:
711:
799:
503:
8:
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Ortiz, Antonio; Killian, J. Antoinette; Verkleij, Arie J.; Wilschut, Jan (October 1999).
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174:, in neurons which triggers the complete fusion of the vesicle with the target membrane.
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551:(Textbook) (7th ed.). Burlington, MA: Elsevier Academic Press. p. 143.
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by calcium, several SNARE complexes come together to form a ring structure, with
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102:
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from secretory vesicles, where their contents are expelled from the cell through
362:
735:"The Mechanism of Vesicle Fusion as Revealed by Molecular Dynamics Simulations"
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200:
Assembly of the SNAREs into the "trans" complexes likely bridges the opposing
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is in position it must wait until Ca enters the cell by the propagation of an
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to the presynaptic membrane. Ca binds to specific proteins, one of which is
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24:
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137:
47:, the universal secretory machinery in cells. Vesicle fusion may depend on
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357:
321:
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Nanavati, C; Markin, V S; Oberhauser, A F; Fernandez, J M (1992-10-01).
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63:
Stimuli that trigger vesicle fusion act by increasing intracellular Ca.
35:. Vesicles can also fuse with other target cell compartments, such as a
460:
191:
40:
32:
651:
336:. It is also proposed that the vesicle does not need to return to an
232:
formation are the lipid-lined and protein-lined fusion pore theories.
213:
209:, with membrane lipids and/or the partially assembled SNARE complex.
28:
594:. Nano and Microengineering Series. CRC Press. pp. 17–1–17–41.
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52:
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636:"Complexin cross-links prefusion SNAREs into a zigzag array"
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inactivated, so that the vesicle is then free to fuse.
788:"The exocytotic fusion pore modeled as a lipidic pore"
700:
Annual Review of
Biophysics and Biomolecular Structure
424:
Medical
Physiology: A Cellular And Molecular Approaoch
421:
401:. Hagerstwon, MD: Lippincott Williams & Wilkins.
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to increase Ca. Examples of this mechanism include:
261:
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394:
392:
733:Marrink, Siewert J.; Mark, Alan E. (2003-09-01).
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274:forming the pore in the vesicle membrane and
27:. In the latter case, it is the end stage of
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387:
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51:in the presence of increased intracellular
320:. The controversy lies in whether or not
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906:
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659:
640:Nature Structural & Molecular Biology
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449:Journal of Bioenergetics and Biomembranes
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742:Journal of the American Chemical Society
712:10.1146/annurev.biophys.35.040405.101958
239:
224:Based on the stability of the resultant
190:
156:
592:Nano and Molecular Electronics Handbook
365:used as models for artificial cells in
212:One hypothesis implicates the molecule
19:is the merging of a vesicle with other
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283:has been observed with as few as two.
148:in the structure of the biomembranes.
85:, many hormones are released by their
78:that cause influx of Ca into the cell.
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781:
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136:Model systems consisting of a single
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426:. Elsevier/Saunders. p. 1300.
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76:voltage-dependent calcium channels
14:
1004:
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74:reaching the synapse, activating
913:Woodbury DJ, Rognlien K (2000).
304:in the membrane fusion process.
262:Protein-lined fusion pore theory
181:SNARE protein and pore formation
131:
119:Growth hormone releasing hormone
970:
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874:10.1523/JNEUROSCI.3983-14.2015
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565:
540:
483:
440:
422:Walter F., PhD. Boron (2003).
236:Lipid-lined fusion pore theory
109:Gonadotropin releasing hormone
1:
812:10.1016/s0006-3495(92)81679-x
516:10.1016/S0006-3495(99)77041-4
373:
334:clathrin-mediated endocytosis
151:
121:(minor pathway - main one is
114:Thyrotropin releasing hormone
7:
862:The Journal of Neuroscience
393:Costanzo, Linda S. (2007).
346:
91:G protein coupled receptors
70:commit vesicle fusion by a
58:
10:
1009:
976:Piginio et al. pp. 161-162
922:Cell Biology International
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600:10.1201/9781315221670-17
358:Presynaptic active zone
308:Kiss-and-run hypothesis
934:10.1006/cbir.2000.0631
246:
197:
123:cAMP dependent pathway
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185:Further information:
157:Synaptic cleft fusion
55:(Ca) concentration.
804:1992BpJ....63.1118N
792:Biophysical Journal
748:(37): 11144–11145.
580:Pigino et al. p.143
571:Pigino et al. p 158
508:1999BpJ....77.2003O
496:Biophysical Journal
326:kiss-and-run fusion
685:"Synapse Function"
461:10.1007/BF00762944
247:
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87:releasing hormones
868:(14): 5772–5780.
754:10.1021/ja036138+
683:Richmond, Janet.
652:10.1038/nsmb.2101
609:978-0-8493-8528-5
558:978-0-12-088397-4
433:978-1-4160-2328-9
408:978-0-7817-7311-9
314:synaptic vesicles
226:cis-SNARE complex
101:, activating the
68:Synaptic vesicles
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17:Vesicle fusion
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230:fusion pore
89:binding to
963:2009-05-31
397:Physiology
374:References
152:Mechanisms
41:Exocytosis
33:exocytosis
882:0270-6474
820:0006-3495
762:0002-7863
618:199021983
363:Liposomes
214:Complexin
29:secretion
987:Category
950:37732173
942:11067766
900:25855187
770:16220905
720:16689631
670:21785414
534:10512820
369:studies.
347:See also
338:endosome
291:Syntaxin
288:in vitro
276:Syntaxin
196:zipping.
59:Triggers
45:porosome
37:lysosome
21:vesicles
891:4388931
838:1420930
829:1262250
800:Bibcode
661:3410656
525:1300481
504:Bibcode
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302:agonist
81:In the
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245:pore.
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