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Synaptic fusion

Choi et al 2003 Proposes LTP might be due to changing glutamate concentrations in the cleft and that the time scale of glutamate release might shift AMPA:NMDA activation ratio. Proposes fusion pore modulation as a mechanism by which time course could be altered.
Doherty & McMahon 2009 Review: difficult to deplete clathrin/AP2, there are several forms of clathrin mediated endocytosis. Affinity for AP may determine recycling/degradation of protein. Clathrin independent pathways need higher Ca. PIP2 is needed for clathrin pit invagination
Jahn & Fasshauer 2012 Review: Strength of interactions between SNAREs disagrees with the vesicle being held, primed and partially zippered, just off the membrane. SNAREs may only bind after the Ca signal. Difficult to reconcile fusion pores & SNAREs (which seem irreversible).
Khanin et al 1997 To generate viable conc of transmitter through a pore discharge must be fast <100ms. Transmitters usually charged, electrical build up would slow release. Co-release with opposite charged molecule or exchange with ion of same charge would incr speed.
Klyachko & Jackson 2002 Showed capacitance flickers (up & down-steps of same size within 2 seconds. Occured after 5% of up-steps. Small microvesicles have smaller pores, this would mean release was too slow, requires a mechanism to incr speed. Pores present but too stable.
McNew et al 2000 Certain v-SNAREs are specific for certain t-SNAREs. Used different combinations of 3 v-SNAREs and 3 t-SNAREs to see which worked. Specificity allows specific SNAREs for intracellular transport. Plasma membrane t-SNARES a little less specific than ER/golgi
Shi et al 2012 Used nanodiscs (17nm membrane patch within scaffold protein ring). Showed by lipid-mixing and Ca release from vesicles that 1 SNARE per nanodisc allows fusion, for the pore to remain open for any time (>10us) you need 3 SNAREs per disc.
Shneider et al 2012 A rapidly expanding pore could accomodate sufficient diffusion for larger vesicles/pores. Smaller pores require a different mechanism, proposes a microjet due to pressure in the vesicle.
Stein et al 2007 SNARE complexes contain 4 SNARE proteins, fusion begins at N terminus. Formation of 2:1 syntaxin:SNAP25 complexes slows zippering, 2nd syntaxin must be displaced for syn'brevin to bind. Synaptotagmin binds acidic phospholipids in opposing membranes
Fernandez et al 1984 Flickering changes in membrane capacitance (measure of surface area). Used mast cells (larger vesicles). Patch-clamping dialyses cellular contents, and infrequency of flicker questioned physiological relevance. Capacitance increases fit with vesicle size
de Toledo et al 1993 Used carbon fibre amperometry to show neurotransmitter release during the flicker. Only a fraction of vesicle contents were released, but this may be because such large vesicles were used (used beige mouse mast cells - 50x larger vesicles than wt).
Wang et al 2003 Showed that pores formed before a full dilation differ in conductance from pores dedicated to kiss-and-run. Strongly indicates different mechanisms operating for each type. Similar regulation of both (incr in one tended to mean an incr in the other).
Ales et al 1999 Showed two types of kiss-and-run. One had a low conductance (similar to Wang 2003). The other caused a spike of release just before closing, indicating a brief dilation. Showed full fusion occurred more at low calcium, kiss-&-run dominating at higher Ca.
Ghandi & Stevens 2003 Marked vesicles of hippocamp neurons with synaptopHluorin. Fluorescence when vesicle opens to cause pH rise, quenched on reacidifcation after retrieval. Retrieval in 400-860ms depending on reacidification speed. Less kiss-&-run at high Ca (contentious).
Granseth et al 2006 SypHy used to show acidification of vesicles on docking. Only saw slow recapture, claims Ghandi 2003 saw flickers of dye moving in and out of frame. Slow recovery inhibited by knockdown of clathrin. Claims no kiss-&-run in hippocampal neurons.
Atluri & Ryan 2006 Showed that reacidification of vesicles takes 3-4 seconds; which limits the validity of synaptopHluorin and sypHy experiments. Did use puffs of acid to quench membrane dye; which may have damaged cell (aimed to leave only endocytosed dye fluorescing.
Zhang et al 2007 Tsien study: Labelled vesicles with small dye & quantum dot. Some vesicles extruded dye w/o losing dot. Dye loss occurred w/ same kinetics w/ or w/o Q dots (which were lost w/ constant kinetics). Q dots may be membrane associated & re-endocytosed (issue)
Han et al 2004 Reduced the conductance of the fusion pore by mutating syntaxin residues (protein lined pore). 3 residues reduced the pore when mutated, all on one side of helix. Reductions are minimal and hasnt been backed up since (consensus is lipid lining).
Monck et al 1990 Showed that the up and down stages of the flickers werent exactly equal indicating that some of the vesicle was left in the membrane. Implies lipid mixing (meaning the pore is at least part lipid)
Oberhauser et al 1992 Non-linear temperature dependence of pore open-time/tendency to collapse open. Indicates that membrane is slightly solidified by temp reduction (would affect a lipid pore far more than a protein lined pore). 1 type of k&r, Ales99 & Wang03 showed 2 types?
Steyer et al 1997 Used TIRF in chromaffin cells, labelled all vesicles but only observed a few. Vesicle mobility drops on vesicle approach, also show wobbling as if tethered. Tethering appears reversible (supports kiss-&-run).
Edwardson et al 2003 PC12 cells expressing a pathological huntingtin fragment showed reduced and redistributed complexin II and reduced exocytosis. Increasing levels of complexin II (long term, not acutely) rescued the phenotype (incr complexin I was detrimental).
Mellander et al 2012 Shows pre and post-spike feet, indicates a small pore which shifts to a larger diameter conformation before returning to a smaller diameter. Used amperometry in PC12 cells
Parisotto et al 2012 Proposes a model in which synaptotagmin docks vesicles ind of Ca. Munc-18 then primes this complex to begin zippering. Partial zippering stabilised & halted by complexin, which is displaced by Ca-syt to allow full zippering.
Created by: Jonmassie



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