Thierry Galli^1* and Volker Haucke^2*

¹Membrane Traffic and Neuronal Plasticity Group, INSERM U536, Institut du Fer-à-moulin, 75005 Paris, France.
²Institut für Chemie-Biochemie, Freie Universität Berlin, D-14195 Berlin, Germany.

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*Corresponding authors. E-mail, thierry{at}tgalli.net (T.G.) or vhaucke{at}chemie.fu-berlin.de (V.H.)

Animation 1. Slow track for synaptic vesicle retrieval by clathrin-mediated endocytosis. The animation illustrates the recruitment, calcium-triggered fusion, and clathrin-mediated endocytosis of synaptic vesicles. Vesicles are recruited from the reserve pool that corresponds to synaptic vesicles attached to the actin cytoskeleton via synapsin. The animation shows the sequential binding of Munc18 and Munc13 to syntaxin as part of the priming process, formation of a loose SNARE complex, and calcium-triggered formation of a tight SNARE complex, followed by vesicle fusion with the plasma membrane and release of neurotransmitter. Clathrin-mediated endocytosis proceeds following targeting of adaptor proteins to membranes enriched in phosphatidylinositol 4,5 bisphate (PIP2). Dynamin then catalyzes the fission of the emanating vesicle from the membrane. Free clathrin-coated vesicles are subsequently uncoated by hsc70, auxilin, while the vesicle PIP2 is hydrolyzed by synaptojanin in conjunction with endophilin. Finally, the proton pump restores the electrochemical gradient (not shown) and the vesicles are refilled with neurotransmitter and can re-enter the cycle.

Use the buttons to proceed through the animation, to step back, or to restart.

The animation was created by Cameron Slayden under the direction of Thierry Galli and Volker Haucke.

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Animation 2. A fast track for synaptic vesicle cycling. In contrast to the slow track, in the fast track, the synaptic vesicles stay in close proximity to the plasma membrane. The animation shows vesicle attachment through loose SNARE complexes between synaptobrevin, syntaxin1, and SNAP-25. Calcium entry triggers a conformational change in synaptotagmin 1 that promotes the formation of a tight SNARE complex, which leads to the hemifusion stage of lipid bilayer fusion followed by the opening of a lipid-made fusion pore and release of neurotransmitter. An unknown mechanism prevents the SNARE complex from dissociating further, thus preventing full fusion and concomitant insertion of synaptic vesicle proteins into the presynaptic plasma membrane. SNAPs (not shown) and NSF catalyze the reversion of tight complexes into incompletely disassembled SNARE complexes, and conformational changes in dynamin close the lipid-made fusion pore.

Use the buttons to proceed through the animation, to step back, or to restart.

The animation was created by Cameron Slayden under the direction of Thierry Galli and Volker Haucke.

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Technical Details

Format: Shockwave Flash Objects (swf file)

Size: 213 kb (Animation 1) or 71 kb (Animation 2)

Requirements: This animation will play with Macromedia Flash 5 or higher (http://www.macromedia.com/downloads/).

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Citation: T. Galli, V. Haucke, Cycling of synaptic vesicles: How far? How fast? Sci. STKE 2004, re19 (2004).

© 2004 American Association for the Advancement of Science