Synaptic Vesicle Fusion Followed by Clathrin-Mediated Endocytosis
1Membrane Traffic and Neuronal Plasticity Group, INSERM U536, Institut du Fer-�-moulin, 75005 Paris, France.
2Zentrum Biochemie & Molekulare Zellbiologie, University of G�ttingen, D-37073 G�ttingen, Germany.
3Science'sSTKE, American Association for the Advancement of Science, 1200 New York Avenue, N.W., Washington, DC 20005, USA.
*Corresponding author. E-mail:
The animation shows calcium-stimulated exocytosis of synaptic vesicles followed by clathrin-mediated vesicle recycling. Many of the molecular components that are involved in synaptic vesicle priming, docking, fusion, and endocytosis are shown. The synaptic vesicles from the reserve pool of vesicles attached to the actin cytoskeleton by synapsin translocate to the vicinity of the plasma membrane and undergo priming through an unknown mechanism in which nSec1 and Munc13, two syntaxin-binding proteins, could participate. This step could lead to the formation of a complex between a synaptic vesicle SNARE (synaptobrevin) and SNAP-25, a plasma membrane target SNARE. Formation of loose SNARE complexes between synaptobrevin, SNAP-25, and syntaxin 1 reduces the distance between the synaptic vesicle and the plasma membrane, allowing docking of the vesicle at the plasma membrane. Entry of calcium could trigger a conformational change in synaptotagmin 1 that would allow further zippering of the SNARE complex into a tight state, which would lead to lipid bilayer fusion. The SNARE complexes, which have been inserted into the plasma membrane, are dissociated by the action of SNAPs (not shown for simplicity) and NSF. Synaptic vesicle proteins are then reinternalized by a clathrin- and dynamin-dependent mechanism at the plasma membrane or at the tip of endosome-like invaginations of the plasma membrane. Dynamin catalyzes the fission of the emanating vesicle from the membrane. Free clathrin-coated vesicles are subsequently uncoated by Hsp70, auxilin, and, possibly, synaptojanin. Finally, the proton pump restores the electrochemical gradient, allowing for the uptake of neurotransmitter into the vesicle. This last step leads to a reformed synaptic vesicle that can reenter the cycle. For simplicity, only the components involved in the action at any given time are shown.
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This animation was created based on Fig. 1 in the Review by Galli and Haucke (see below) and was prepared by Cameron Slayden with the scientific oversight of T. Galli and V. Haucke.
Learning Resource Type: Animation
Context: Undergraduate upper division, graduate, professional (degree program)
Intended Users: Teacher, learner
Intended Educational Use: Teach, learn
Discipline: Cell biology, molecular biology, neurobiology, biochemistry
Keywords: movie, signal transduction, neuron, synapse, endocytosis, exocytosis
Format: Shockwave Flash Object (swf file)
Size: 145 kb
Requirements: Macromedia Flash 5 (http://www.macromedia.com/downloads/)
ST on the Web: Educator Sites (http://stke.sciencemag.org/cgi/ul/sigtransUl;CAT_9)--BioSciEdNet (BEN) Portal and Synaptic Transmission: A Four Step Process
Limits for Use
Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for non-commercial, course teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.
Citation: T. Galli, V. Haucke, N. R. Gough, Synaptic vesicle fusion followed by clathrin-mediated endocytosis. Sci. STKE2003, tr3 (2003).