Synaptic Vesicle Traffic

Abstract

Signals travel along nerve cell membranes as electrical impulses but are transmitted from one neuron to other neurons and/or effector cells by the release of neurotransmitter across a small intervening space (synaptic cleft). Such neurotransmitter is contained within synaptic vesicles that fuse with the plasma membrane when it depolarizes, to release their contents. The vesicles are then rapidly retrieved and refurbished to sustain further synaptic activity.

Keywords: neurotransmitter release; synapse physiology; clathrin; dynamin; endocytosis; exocytosis; neurotransmitter; SNARE

Figure 1.

Fusion between synaptic vesicles and nerve terminal plasma membrane. Electron micrograph of a cross‐section of a neuromuscular junction quickly frozen (in less than 10 ms) after a single stimulus. The bracketed area is an active zone, facing a postsynaptic membrane. The arrow indicates a vesicle open to the synaptic cleft through a narrow pore. The arrowhead indicates a vesicle partially fused with the plasma membrane (omega shape). (Micrograph courtesy of F. Torri Tarelli, F. Grohovaz, R. Fesce and B. Ceccarelli.)

Figure 2.

Molecular schemes of synaptic vesicle traffic in nerve terminals. Cytoplasmic (dark blue) and noncytoplasmic (light blue) leaflets of synaptic vesicle and nerve terminal plasma membranes are shown. (a) Three vesicles held in reserve are tethered to actin filaments (dark green) by synapsin proteins (violet). On the vesicle surface, synaptophysin (yellow) interacts with synaptobrevin (red) to prevent its association with target SNARE (soluble N‐ethylmaleimide‐sensitive protein ( NSF) attachment protein (SNAP) receptor) proteins, SNAP‐25 (blue) and syntaxin (orange) in the plasma membrane. Similarly, munc18 (mammalian uncoordinated) (brown) may sequester syntaxin on the plasma membrane. Two other vesicles dock at the plasma membrane via interactions between SNAREs as well as synaptotagmin (light green) and calcium channels (pink). (b) These channels open when action potentials depolarize the nerve terminal to allow Ca2+ entry. Synaptotagmin and SNAREs alter conformation upon Ca2+ binding to promote fusion and neurotransmitter release (white). (c) The vesicle on the right opens transiently to release neurotransmitter through a pore of synaptophysin before resealing and returning to a docked, neurotransmitter‐loaded position. The vesicle on the left collapses completely into the plasma membrane while Ca2+‐induced phosphorylation of synapsin releases a reserve vesicle to replace the collapsed vesicle. In the collapsed vesicle membrane, synaptophysin attracts cholesterol while synaptotagmin attracts adapter proteins that recruit clathrin (black). (d) Clathrin coats the budding vesicle while dynamin (purple) assembles around the neck of the bud to promote fission. (e) The vesicle buds and the clathrin coat disassemble and the vesicle joins the reserve pool.

Figure 3.

Dynamin sits at the endocytotic vesicle fission site in nerve terminals. Electron micrographs of nerve terminal membranes incubated with a nonhydrolysable form of guanosine triphosphate (GTP) before fixation. (a) Cross‐section of a nerve terminal containing many synaptic vesicles and one tubular invagination of the plasma membrane with electron‐dense protein bands along the neck (arrow). (b) A higher magnification view of the invagination in (a). Protein bands cover the neck but not the round head of the invagination. Arrows indicate vesicles coated with clathrin. (c) and (d) Gold particles bound to antibodies identify dynamin surrounding the narrow neck but not the round head of invaginations. Reprinted by permission from Nature (Takei K, McPherson PS, Schmid SL and De Camilli P (1995) Tubular membrane invaginations coated by dynamin rings are induced by GTP‐gamma S in nerve terminals. Nature374: 186–192) copyright (1995) Macmillan Magazines Ltd.

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References

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Further Reading

Betz WJ and Angelson JK (1998) The synaptic vesicle cycle. Annual Review of Physiology 60: 347–363.

Calakos N and Scheller RH (1996) Synaptic vesicle biogenesis, docking, and fusion: a molecular description. Physiological Reviews 76: 1–29.

De Camilli P and Takei K (1996) Molecular mechanisms in synaptic vesicle endocytosis and recycling. Neuron 16: 481–486.

Fernández‐Chacon R and Südhof TC (1999) Genetics of synaptic vesicle function: toward the complete functional anatomy of an organelle. Annual Review of Physiology 61: 753–776.

Kandel ER, Schwartz JH and Jessell TM (2000) Principles of Neural Science, 4th edn. New York: McGraw‐Hill.

Montecucco C (1998) Protein toxins and membrane transport. Current Opinion in Cell Biology 10: 530–536.

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Turner KM, Burgoyne RD and Morgan A (1999) Protein phosphorylation and the regulation of synaptic membrane traffic. Trends in Neuroscience 22(10): 459–464.

von Gersdorff H and Matthews G (1999) Electrophysiology of synaptic vesicle cycling. Annual Review of Physiology 61: 725–752.

Zigmond MJ, Bloom FE, Landis SC, Roberts JL and Squire LR (1999) Fundamental Neuroscience. London: Academic Press.

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Dunlap, David, Valtorta, Flavia, and Fesce, Riccardo(Apr 2001) Synaptic Vesicle Traffic. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000215]