Abstract
Central nerve terminals are placed under considerable stress during intense stimulation due to large numbers of synaptic vesicles (SVs) fusing with the plasma membrane. Classical clathrin-dependent SV endocytosis cannot correct for the large increase in nerve terminal surface area in the short term, due to its slow kinetics and low capacity. During such intense stimulation, an additional SV retrieval pathway is recruited called bulk endocytosis. Recent studies have shown that bulk endocytosis fulfils all of the physiological requirements to remedy the acute changes in nerve terminal surface area to allow the nerve terminal to continue to function. This review will summarise the recent developments in the field that characterise the physiology of bulk endocytosis which show that it is a fast, activity-dependent and high capacity mechanism that is essential for the function of central nerve terminals.
Similar content being viewed by others
References
Royle SJ, Lagnado L (2003) Endocytosis at the synaptic terminal. J Physiol 553:345–355
Murthy VN, De Camilli P (2003) Cell biology of the presynaptic terminal. Ann Rev Neurosci 26:701–728
Granseth B, Odermatt B, Royle SJ, Lagnado L (2006) Clathrin-mediated endocytosis is the dominant mechanism of vesicle retrieval at hippocampal synapses. Neuron 51:773–786
Balaji J, Armbruster M, Ryan TA (2008) Calcium control of endocytic capacity at a CNS synapse. J Neurosci 28:6742–6749
Ceccarelli B, Hurlbut WP, Mauro A (1972) Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation. J Cell Biol 54:30–38
Ceccarelli B, Hurlbut WP, Mauro A (1973) Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. J Cell Biol 57:499–524
Ales E, Tabares L, Poyato JM, Valero V, Lindau M, Alvarez de Toledo G (1999) High calcium concentrations shift the mode of exocytosis to the kiss-and-run mechanism. Nat Cell Biol 1:40–44
Wang CT, Lu JC, Bai J, Chang PY, Martin TF, Chapman ER, Jackson MB (2003) Different domains of synaptotagmin control the choice between kiss-and-run and full fusion. Nature 424:943–947
Oberhauser AF, Fernandez JM (1996) A fusion pore phenotype in mast cells of the ruby-eye mouse. Proc Natl Acad Sci USA 93:14349–14354
He L, Wu LG (2007) The debate on the kiss-and-run fusion at synapses. Trends Neurosci 30:447–455
Richards DA, Guatimosim C, Betz WJ (2000) Two endocytic recycling routes selectively fill two vesicle pools in frog motor nerve terminals. Neuron 27:551–559
Evans GJ, Cousin MA (2007) Activity-dependent control of slow synaptic vesicle endocytosis by cyclin-dependent kinase 5. J Neurosci 27:401–411
Miller TM, Heuser JE (1984) Endocytosis of synaptic vesicle membrane at the frog neuromuscular junction. J Cell Biol 98:685–698
Richards DA, Guatimosim C, Rizzoli SO, Betz WJ (2003) Synaptic vesicle pools at the frog neuromuscular junction. Neuron 39:529–541
Teng H, Wilkinson RS (2000) Clathrin-mediated endocytosis near active zones in snake motor boutons. J Neurosci 20:7986–7993
Leenders AG, Scholten G, de Lange RP, Lopes Da Silva FH, Ghijsen WE (2002) Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals. Neurosci 109:195–206
Marxen M, Volknandt W, Zimmermann H (1999) Endocytic vacuoles formed following a short pulse of K+-stimulation contain a plethora of presynaptic membrane proteins. Neurosci 94:985–996
Di Paolo G, Moskowitz HS, Gipson K, Wenk MR, Voronov S, Obayashi M, Flavell R, Fitzsimonds RM, Ryan TA, De Camilli P (2004) Impaired PtdIns(4, 5) P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking. Nature 431:415–422
Hayashi M, Raimondi A, O'Toole E, Paradise S, Collesi C, Cremona O, Ferguson SM, De Camilli P (2008) Cell- and stimulus-dependent heterogeneity of synaptic vesicle endocytic recycling mechanisms revealed by studies of dynamin 1-null neurons. Proc Natl Acad Sci USA 105:2175–2180
Holt M, Cooke A, Wu MM, Lagnado L (2003) Bulk membrane retrieval in the synaptic terminal of retinal bipolar cells. J Neurosci 23:1329–1339
de Lange RP, de Roos AD, Borst JG (2003) Two modes of vesicle recycling in the rat calyx of Held. J Neurosci 23:10164–10173
Paillart C, Li J, Matthews G, Sterling P (2003) Endocytosis and vesicle recycling at a ribbon synapse. J Neurosci 23:4092–4099
Wu W, Wu LG (2007) Rapid bulk endocytosis and its kinetics of fission pore closure at a central synapse. Proc Natl Acad Sci USA 104:10234–10239
Clayton EL, Evans GJ, Cousin MA (2008) Bulk synaptic vesicle endocytosis is rapidly triggered during strong stimulation. J Neurosci 28:6627–6632
Teng H, Lin MY, Wilkinson RS (2007) Macroendocytosis and endosome processing in snake motor boutons. J Physiol 582:243–262
Sankaranarayanan S, Ryan TA (2000) Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nat Cell Biol 2:197–204
Klee CB, Crouch TH, Krinks MH (1979) Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci USA 76:6270–3
Chan SA, Smith C (2001) Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells. J Physiol 537:871–885
Kumashiro S, Lu YF, Tomizawa K, Matsushita M, Wei FY, Matsui H (2005) Regulation of synaptic vesicle recycling by calcineurin in different vesicle pools. Neurosci Res 51:435–443
Clayton EL, Cousin MA (2008) Differential labelling of bulk endocytosis in nerve terminals by FM dyes. Neurochem Int 53:51–55
Cousin MA, Robinson PJ (2001) The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis. Trends Neurosci 24:659–665
Koenig JH, Ikeda K (1989) Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval. J Neurosci 9:3844–3860
Takei K, Mundigl O, Daniell L, De Camilli P (1996) The synaptic vesicle cycle: A single vesicle budding step involving clathrin and dynamin. J Cell Biol 133:1237–1250
Gad H, Low P, Zotova E, Brodin L, Shupliakov O (1998) Dissociation between Ca2+-triggered synaptic vesicle exocytosis and clathrin-mediated endocytosis at a central synapse. Neuron 21:607–616
Kasprowicz J, Kuenen S, Miskiewicz K, Habets RL, Smitz L, Verstreken P (2008) Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake. J Cell Biol 182:1007–1016
Heerssen H, Fetter RD, Davis GW (2008) Clathrin dependence of synaptic-vesicle formation at the Drosophila neuromuscular junction. Curr Biol 18:401–409
Acknowledgements
This work was supported by grants from the Wellcome Trust (Ref: 070569 & 084277) and Epilepsy Research UK (0503).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cousin, M.A. Activity-Dependent Bulk Synaptic Vesicle Endocytosis—A Fast, High Capacity Membrane Retrieval Mechanism. Mol Neurobiol 39, 185–189 (2009). https://doi.org/10.1007/s12035-009-8062-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-009-8062-3