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Item 3
"Kiss and run" synaptic vesicles?
For almost thirty years there have been two competing hypotheses
about how synaptic vesicles discharge transmitter molecules into
the synapse and then are recycled for further activity. Recent
experiments and reviews indicate that both hypotheses are correct,
each applying to a different pool of vesicles within the presynaptic
terminal (Richards, Guatimosin, and Betz, 2000; Wilkinson and
Cole, 2001).
Heuser and Reese (1973) proposed, on the basis of experimental
evidence, that the membranes of activated synaptic vesicles fuse
with the membrane of the presynaptic terminal at the active zone
(the region of the presynaptic terminal facing the synaptic cleft)
and the vesicles discharge their contents into the synaptic cleft.
Membrane is then taken from a region of the presynaptic terminal
away from the active zone and used to form new vesicles which
are then filled with synaptic transmitter molecules. This is the
account that has been more widely accepted and that is presented
in the text (pp. 73-74) and in the animation of Study Guide tutorial
3.2.
But in the same number of the same journal in which Heuser and
Reese (1973) published their report, another group -- Ceccarelli,
Hurlbut and Mauro (1973) -- proposed another mechanism: A small
part of the membrane of an active vesicle fuses with and forms
a pore through the region of the presynaptic terminal facing the
synaptic cleft and the vesicle discharges transmitter molecules
(but not its entire contents) into the synaptic cleft. After discharging
the transmitter molecules, the intact vesicle then separates from
the membrane of the presynaptic bouton and moves to the interior
of the bouton to have its store of transmitter molecules replenished.
These processes should permit more rapid, sustained synaptic activity
than those reported by Heuser and Reese. This more rapid mechanism
is now referred to as "kiss and run," a term apparently
first proposed in a review by Fesce et al. (1994)
Studying the activity of synaptic vesicles has involved use
of electron microscopy, specialized dyes, and related electrophysiology
(Betz et al., 2000). Research on this question began with the
frog neuromuscular junction and has been extended to other species
and synapses. It now appears that there are two pools of vesicles:
(1) A readily releasable pool of vesicles located at or close
to the active zone of the presynaptic membrane. These are kiss
and run vesicles that reform rapidly after electrical stimulation
of the neuron. (2) A reserve pool of vesicles located away from
the active zone of the presynaptic membrane. These vesicles are
reformed relatively slowly from infolding of the cell membrane.
During intense electrical stimulation of the neuron, vesicles
of the reserve pool are mobilized over 10-15 s and migrate to
the active zone. The relative numbers of vesicles in the two pools
appears to differ in different parts of the nervous system and
to be modulated by extracellular events, so work on these questions
is continuing.
References:
Ceccarelli, B., Hurlbut, W.P. and Mauro, A. (1973). Turnover
of transmitter and synaptic vesicles at the frog neuromuscular
junction. Journal of Cell Biology, 57, 499-524.
Fesce, R., Grohovaz, F., Valtorta, F. and Meldolesi, J. (1994).
Neurotransmitter release: fusion or 'kiss-and-run'? Trends
in Cell Biology, 4, 1-4.
Heuser, J.E. and Reese, T.S. (1973). Evidence for recycling
of synaptic vesicle membrane during transmitter release at the
frog neuromuscular junction. Journal of Cell Biology, 57,
315-344.
Richards, D.A., Guatimosin, C. and Betz, W.T. (2000). Two endocytic
recycling routes selectively fill two vesicle pools in frog motor
nerve terminals. Neuron, 27, 551-559.
Wilkinson, R.S. and Cole, J.C. (2001). Resolving the Heuser-Ceccarelli
debate. Trends in Neuroscience, 24, 195-197.
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