Synaptic Vesicle Traffic

David Dunlap, San Raffaele Scientific Institute, Milan, Italy
Flavia Valtorta, San Raffaele Scientific Institute, Milan, Italy
Riccardo Fesce, National Research Council, Milan, Italy

Published online: April 2001

DOI: 10.1038/npg.els.0000215

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. Nature 374: 186–192) copyright (1995) Macmillan Magazines Ltd.
close
 References
    Alès E, Tabares L, Poyato JM et al. (1999) High calcium concentrations shift the mode of exocytosis to the kiss-and-run mechanism. Nature Cell Biology 1: 40–44.
    Ceccarelli B, Hurlbut WP and Mauro A (1973) Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. Journal of Cell Biology 57: 499–524.
    Couteaux R and Pecot-De Chavassine M (1970) [Synaptic vesicles and pouches at the level of ‘active zones’ of the neuromuscular junction]. Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences D: Sciences Naturelles 271: 2346–2349.[In French.]
    De Robertis EDP and Bennet HS (1955) Some features of the submicroscopic morphology of synapses in frog and earthworm. Journal of Biophysics and Biochemical Cytology 1: 47–58.
    Del Castillo J and Katz B (1956) Biophysical aspects of neuro-muscular transmission. Progress in Biophysics and Biophysical Chemistry 6: 121–170.
    Greengard P, Valtorta F, Czernik AJ and Benfenati F (1993) Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 259: 780–785.
    Heuser JE and Reese TS (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. Journal of Cell Biology 57: 315–344.
    McIntire SL, Jorgensen E and Horvitz HR (1992) Genes required for GABA function in Caenorhabditis elegans. Nature 364: 334–337.
    Palay SL (1956) Synapses in the central nervous system. Journal of Biophysics and Biochemical Cytology 2(Supplement): 193–202.
    Sankaranarayanan S and Ryan TA (2000) Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nature Cell Biology 2(4): 197–204.
    Takei K, McPherson PS, Schmid SL and De Camilli P (1995) Tubular membrane invaginations coated by dynamin rings are induced by GTP-S in nerve terminals. Nature 374: 186–192.
    Thiele C, Hannah MJ, Fahrenholz F and Huttner WB (1999) Cholesterol binds to synaptophysin and is required for bigenesis of synaptic vesicles. Nature Cell Biology 2: 42–49.
    Valtorta F, Jahn R, Fesce R, Greengard P and Ceccarelli B (1988) Synaptophysin (p38) at the frog neuromuscular junction: its incorporation into the axolemma and recycling after intense quantal secretion. Journal of Cell Biology 107: 2717–2727.
 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.
    book 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.
    Rothman JE and Warren G (1994) Implications of the SNARE hypothesis for intracellular membrane topology and dynamics. Current Biology 4: 220–233.
    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.
    book Zigmond MJ, Bloom FE, Landis SC, Roberts JL and Squire LR (1999) Fundamental Neuroscience. London: Academic Press.

Related Sub-Topics:

Neurotransmitters | Synaptic Transmission | Cell Membranes
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Synaptic Vesicle Traffic
 
How to Cite close
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]