Key Points
-
Nervous system function crucially depends on synaptic vesicle exocytosis and endocytosis at defined areas within the nerve terminal. Exocytosis preferentially occurs at defined release sites within the active zone, whereas synaptic vesicle membranes are retrieved largely from the surrounding periactive zone.
-
Release may be limited by a given fixed number of release sites that need to be cleared prior to the next presynaptic fusion event. This release site clearance is likely to be of physiological importance, for example, during short-term plasticity.
-
Evidence from the calyx of Held synapse shows that interference with endocytic protein function causes defects in short-term plasticity, and hence, in release site clearance. This indicates that synaptic vesicle exocytosis and endocytosis are tightly coupled.
-
Multidomain proteins of the active and surrounding periactive zones are potential scaffolds that couple exocytic fusion to the clearance of release sites.
-
Possible models regarding the mechanism by which release sites are cleared may involve lateral diffusion or removal of clustered synaptic vesicle proteins and/or dynamin-mediated membrane remodelling.
Abstract
Mechanisms that ensure robust long-term performance of synaptic transmission over a wide range of activity are crucial for the integrity of neuronal networks, for processing sensory information and for the ability to learn and store memories. Recent experiments have revealed that such robust performance requires a tight coupling between exocytic vesicle fusion at defined release sites and endocytic retrieval of synaptic vesicle membranes. Distinct presynaptic scaffolding proteins are essential for fulfilling this requirement, providing either ultrastructural coordination or acting as signalling hubs.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kopp-Scheinpflug, C., Tolnai, S., Malmierca, M. S. & Rubsamen, R. The medial nucleus of the trapezoid body: comparative physiology. Neuroscience 154, 160–170 (2008).
Taschenberger, H. & von Gersdorff, H. Fine-tuning an auditory synapse for speed and fidelity: developmental changes in presynaptic waveform, EPSC kinetics, and synaptic plasticity. J. Neurosci. 20, 9162–9173 (2000).
Gundelfinger, E. D., Kessels, M. M. & Qualmann, B. Temporal and spatial coordination of exocytosis and endocytosis. Nature Rev. Mol. Cell Biol. 4, 127–139 (2003).
Katz, B. & Miledi, R. Spontaneous and evoked activity of motor nerve endings in calcium Ringer. J. Physiol. 203, 689–706 (1969).
Neher, E. & Sakaba, T. Multiple roles of calcium ions in the regulation of neurotransmitter release. Neuron 59, 861–872 (2008).
Dittman, J. & Ryan, T. A. Molecular circuitry of endocytosis at nerve terminals. Annu. Rev. Cell Dev. Biol. 25, 133–160 (2009).
Galli, T. & Haucke, V. Cycling of synaptic vesicles: how far? How fast! Sci. STKE, re19 (2004).
Murthy, V. N. & De Camilli, P. Cell biology of the presynaptic terminal. Annu. Rev. Neurosci. 26, 701–728 (2003).
Neher, E. What is rate-limiting during sustained synaptic activity: vesicle supply or availability of release sites? FNSYN 2, 1–6 (2010).
Smith, S. M., Renden, R. & von Gersdorff, H. Synaptic vesicle endocytosis: fast and slow modes of membrane retrieval. Trends Neurosci. 31, 559–568 (2008).
Granseth, B., Odermatt, B., Royle, S. J. & Lagnado, L. Clathrin-mediated endocytosis is the dominant mechanism of vesicle retrieval at hippocampal synapses. Neuron 51, 773–786 (2006).
Martens, S. & McMahon, H. T. Mechanisms of membrane fusion: disparate players and common principles. Nature Rev. Mol. Cell Biol. 9, 543–556 (2008).
Jahn, R. & Scheller, R. H. SNAREs — engines for membrane fusion. Nature Rev. Mol. Cell Biol. 7, 631–643 (2006).
Doherty, G. J. & McMahon, H. T. Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857–902 (2009).
Katz, B. Quantal mechanism of neural transmitter release. Science 173, 123–126 (1971).
Takamori, S. et al. Molecular anatomy of a trafficking organelle. Cell 127, 831–846 (2006).
Rizzoli, S. O. & Betz, W. J. Synaptic vesicle pools. Nature Rev. Neurosci. 6, 57–69 (2005).
Kim, S. H. & Ryan, T. A. CDK5 serves as a major control point in neurotransmitter release. Neuron 67, 797–809 (2010).
Ikeda, K. & Bekkers, J. M. Counting the number of releasable synaptic vesicles in a presynaptic terminal. Proc. Natl Acad. Sci. USA 106, 2945–2950 (2009).
Kuromi, H. & Kidokoro, Y. Two distinct pools of synaptic vesicles in single presynaptic boutons in a temperature-sensitive Drosophila mutant, shibire. Neuron 20, 917–925 (1998).
Murthy, V. N. & Stevens, C. F. Reversal of synaptic vesicle docking at central synapses. Nature Neurosci. 2, 503–507 (1999).
Sigrist, S. J. & Schmitz, D. Structural and functional plasticity of the cytoplasmic active zone. Curr. Opin. Neurobiol. 8 Sep 2010 (doi:10.1016/j.conb.2010.08.012).
Sudhof, T. C. & Rothman, J. E. Membrane fusion: grappling with SNARE and SM proteins. Science 323, 474–477 (2009).
Mohrmann, R., de Wit, H., Verhage, M., Neher, E. & Sorensen, J. B. Fast vesicle fusion in living cells requires at least three SNARE complexes. Science 330, 502–505 (2010).
van den Bogaart, G. et al. One SNARE complex is sufficient for membrane fusion. Nature Struct. Mol. Biol. 17, 358–364 (2010).
Hui, E., Johnson, C. P., Yao, J., Dunning, F. M. & Chapman, E. R. Synaptotagmin-mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion. Cell 138, 709–721 (2009).
Xue, M. et al. Distinct domains of complexin I differentially regulate neurotransmitter release. Nature Struct. Mol. Biol. 14, 949–958 (2007).
Wang, X. et al. A protein interaction node at the neurotransmitter release site: domains of Aczonin/Piccolo, Bassoon, CAST, and rim converge on the N-terminal domain of Munc13-1 J. Neurosci. 29, 12584–12596 (2009).
Kittel, R. J. et al. Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 312, 1051–1054 (2006). Loss of function of the active zone protein BRP in Drosophila melanogaster is shown to disrupt active zone assembly and cause defects in calcium channel clustering and presynaptic release.
Leal-Ortiz, S. et al. Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis. J. Cell Biol. 181, 831–846 (2008).
Zenisek, D., Steyer, J. A. & Almers, W. Transport, capture and exocytosis of single synaptic vesicles at active zones. Nature 406, 849–854 (2000).
Wu, L. G., Ryan, T. A. & Lagnado, L. Modes of vesicle retrieval at ribbon synapses, calyx-type synapses, and small central synapses. J. Neurosci. 27, 11793–11802 (2007).
Xu, J. et al. GTP-independent rapid and slow endocytosis at a central synapse. Nature Neurosci. 11, 45–53 (2008).
Hosoi, N., Holt, M. & Sakaba, T. Calcium dependence of exo- and endocytotic coupling at a glutamatergic synapse. Neuron 63, 216–229 (2009). Elegant work focusing on the calyx of Held, showing that interference with endocytic protein function causes short-term depression indicating defective exocytic–endocytic coupling.
Renden, R. & von Gersdorff, H. Synaptic vesicle endocytosis at a CNS nerve terminal: faster kinetics at physiological temperatures and increased endocytotic capacity during maturation. J. Neurophysiol. 98, 3349–3359 (2007).
Smith, C. & Neher, E. Multiple forms of endocytosis in bovine adrenal chromaffin cells. J. Cell Biol. 139, 885–894 (1997).
Balaji, J. & Ryan, T. A. Single-vesicle imaging reveals that synaptic vesicle exocytosis and endocytosis are coupled by a single stochastic mode. Proc. Natl Acad. Sci. USA 104, 20576–20581 (2007).
Sankaranarayanan, S. & Ryan, T. A. Calcium accelerates endocytosis of vSNAREs at hippocampal synapses. Nature Neurosci. 4, 129–136 (2001).
Sankaranarayanan, S. & Ryan, T. A. Real-time measurements of vesicle-SNARE recycling in synapses of the central nervous system. Nature Cell Biol. 2, 197–204 (2000).
Holt, M., Cooke, A., Wu, M. M. & Lagnado, L. Bulk membrane retrieval in the synaptic terminal of retinal bipolar cells. J. Neurosci. 23, 1329–1339 (2003).
Clayton, E. L. et al. Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles. Nature Neurosci. 13, 845–851 (2010).
Geumann, U., Schafer, C., Riedel, D., Jahn, R. & Rizzoli, S. O. Synaptic membrane proteins form stable microdomains in early endosomes. Microsc. Res. Tech. 73, 606–617 (2010).
Krauss, M. & Haucke, V. Adaptin' endosomes for synaptic vesicle recycling, learning and memory. EMBO J. 29, 1313–1315 (2010).
Fernandez-Alfonso, T., Kwan, R. & Ryan, T. A. Synaptic vesicles interchange their membrane proteins with a large surface reservoir during recycling. Neuron 51, 179–186 (2006).
Wienisch, M. & Klingauf, J. Vesicular proteins exocytosed and subsequently retrieved by compensatory endocytosis are nonidentical. Nature Neurosci. 9, 1019–1027 (2006).
Willig, K. I., Rizzoli, S. O., Westphal, V., Jahn, R. & Hell, S. W. STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis. Nature 440, 935–939 (2006).
Opazo, F. et al. Limited intermixing of synaptic vesicle components upon vesicle recycling. Traffic 11, 800–812 (2010). References 44–47 are a controversial set of papers pertaining to the question of whether newly exocytosed synaptic vesicle proteins remain clustered or intermix with a pre-existing pool on the neuronal plasma membrane.
Ferguson, S. M. et al. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis. Science 316, 570–574 (2007).
Heerssen, H., Fetter, R. D. & Davis, G. W. Clathrin dependence of synaptic-vesicle formation at the Drosophila neuromuscular junction. Curr. Biol. 18, 401–409 (2008).
Kasprowicz, J. et al. Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake. J. Cell Biol. 182, 1007–1016 (2008).
Koenig, J. H. & Ikeda, K. Synaptic vesicles have two distinct recycling pathways. J. Cell Biol. 135, 797–808 (1996).
Kim, S. H. & Ryan, T. A. Synaptic vesicle recycling at CNS snapses without AP-2. J. Neurosci. 29, 3865–3874 (2009).
Diril, M. K., Wienisch, M., Jung, N., Klingauf, J. & Haucke, V. Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling. Dev. Cell 10, 233–244 (2006).
Maritzen, T., Podufall, J. & Haucke, V. Stonins — specialized adaptors for synaptic vesicle recycling and beyond? Traffic 11, 8–15 (2010).
Jung, N. & Haucke, V. Clathrin-mediated endocytosis at synapses. Traffic 8, 1129–1136 (2007).
Wenk, M. R. & De Camilli, P. Protein–lipid interactions and phosphoinositide metabolism in membrane traffic: insights from vesicle recycling in nerve terminals. Proc. Natl Acad. Sci. USA 101, 8262–8269 (2004).
McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005).
Ferguson, S. M. et al. Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev. Cell 17, 811–822 (2009).
Slepnev, V. I. & De Camilli, P. Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nature Rev. Neurosci. 1, 161–172 (2000).
Marie, B. et al. Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth. Neuron 43, 207–219 (2004).
Koh, T. W., Verstreken, P. & Bellen, H. J. Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis. Neuron 43, 193–205 (2004).
Pechstein, A., Shupliakov, O. & Haucke, V. Intersectin 1: a versatile actor in the synaptic vesicle cycle. Biochem. Soc. Trans. 38, 181–186 (2010).
Shupliakov, O. et al. Synaptic vesicle endocytosis impaired by disruption of dynamin–SH3 domain interactions. Science 276, 259–263 (1997).
Ringstad, N. et al. Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron 24, 143–154 (1999).
Dickman, D. K., Horne, J. A., Meinertzhagen, I. A. & Schwarz, T. L. A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin. Cell 123, 521–533 (2005).
Qualmann, B., Roos, J., DiGregorio, P. J. & Kelly, R. B. Syndapin I, a synaptic dynamin-binding protein that associates with the neural Wiskott-Aldrich syndrome protein. Mol. Biol. Cell 10, 501–513 (1999).
Rao, Y. et al. Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation. Proc. Natl Acad. Sci. USA 107, 8213–8218 (2010).
Bloom, O. et al. Colocalization of synapsin and actin during synaptic vesicle recycling. J. Cell Biol. 161, 737–747 (2003).
Sankaranarayanan, S., Atluri, P. P. & Ryan, T. A. Actin has a molecular scaffolding, not propulsive, role in presynaptic function. Nature Neurosci. 6, 127–135 (2003).
Candiani, S. et al. The synapsin gene family in basal chordates: evolutionary perspectives in metazoans. BMC Evol. Biol. 10, 32 (2010).
Pechstein, A. et al. Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2. Proc. Natl Acad. Sci. USA 107, 4206–4211 (2010).
Koh, T. W. et al. Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development. J. Cell Biol. 178, 309–322 (2007).
Henne, W. M. et al. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science 328, 1281–1284 (2010).
Gad, H., Low, P., Zotova, E., Brodin, L. & Shupliakov, O. Dissociation between Ca2+-triggered synaptic vesicle exocytosis and clathrin-mediated endocytosis at a central synapse. Neuron 21, 607–616 (1998). In this paper, work at the lamprey reticulospinal synapse reveals calcium regulation of synaptic vesicle endocytosis and a potential role for calcium in exocytic–endocytic coupling.
Teng, H., Cole, J. C., Roberts, R. L. & Wilkinson, R. S. Endocytic active zones: hot spots for endocytosis in vertebrate neuromuscular terminals. J. Neurosci. 19, 4855–4866 (1999).
Yao, C. K. et al. A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis. Cell 138, 947–960 (2009).
Deak, F., Schoch, S., Liu, X., Sudhof, T. C. & Kavalali, E. T. Synaptobrevin is essential for fast synaptic-vesicle endocytosis. Nature Cell Biol. 6, 1102–1108 (2004).
Nicholson-Tomishima, K. & Ryan, T. A. Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin, I. Proc. Natl Acad. Sci. USA 101, 16648–16652 (2004).
Yao, J., Nowack, A., Kensel-Hammes, P., Gardner, R. G. & Bajjalieh, S. M. Cotrafficking of SV2 and synaptotagmin at the synapse. J. Neurosci. 30, 5569–5578 (2010).
Poskanzer, K. E., Marek, K. W., Sweeney, S. T. & Davis, G. W. Synaptotagmin I is necessary for compensatory synaptic vesicle endocytosis in vivo. Nature 426, 559–563 (2003).
Wadel, K., Neher, E. & Sakaba, T. The coupling between synaptic vesicles and Ca2+ channels determines fast neurotransmitter release. Neuron 53, 563–575 (2007).
Yang, Y. M. et al. Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse. Neuron 67, 100–115 (2010).
Kawasaki, F., Hazen, M. & Ordway, R. W. Fast synaptic fatigue in shibire mutants reveals a rapid requirement for dynamin in synaptic vesicle membrane trafficking. Nature Neurosci. 3, 859–860 (2000). This paper shows that mutational inactivation of dynamin in Drosophila results in synaptic fatigue, in spite of a full complement of synaptic vesicles, indicating a potential function for dynamin in exocytic–endocytic coupling.
Kawasaki, F. & Ordway, R. W. Molecular mechanisms determining conserved properties of short-term synaptic depression revealed in NSF and SNAP-25 conditional mutants. Proc. Natl Acad. Sci. USA 106, 14658–14663 (2009).
Fenster, S. D. et al. Interactions between Piccolo and the actin/dynamin-binding protein Abp1 link vesicle endocytosis to presynaptic active zones. J. Biol. Chem. 278, 20268–20277 (2003).
Chen, Y. et al. Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis. Cell 115, 37–48 (2003).
Lai, M. M. et al. The calcineurin-dynamin 1 complex as a calcium sensor for synaptic vesicle endocytosis. J. Biol. Chem. 274, 25963–25966 (1999).
Liu, J. P., Sim, A. T. & Robinson, P. J. Calcineurin inhibition of dynamin I GTPase activity coupled to nerve terminal depolarization. Science 265, 970–973 (1994).
Daly, C. & Ziff, E. B. Ca2+-dependent formation of a dynamin-synaptophysin complex: potential role in synaptic vesicle endocytosis. J. Biol. Chem. 277, 9010–9015 (2002).
Henkel, A. W. & Betz, W. J. Monitoring of black widow spider venom (BWSV) induced exo- and endocytosis in living frog motor nerve terminals with FM1–43 Neuropharmacology 34, 1397–406 (1995).
Kuromi, H. & Kidokoro, Y. Selective replenishment of two vesicle pools depends on the source of Ca2+ at the Drosophila synapse. Neuron 35, 333–343 (2002).
Zefirov, A. L., Abdrakhmanov, M. M., Mukhamedyarov, M. A. & Grigoryev, P. N. The role of extracellular calcium in exo- and endocytosis of synaptic vesicles at the frog motor nerve terminals. Neuroscience 143, 905–910 (2006).
Kuromi, H., Honda, A. & Kidokoro, Y. Ca2+ influx through distinct routes controls exocytosis and endocytosis at drosophila presynaptic terminals. Neuron 41, 101–111 (2004). This paper provides evidence in favour of distinct types of calcium channels that regulate synaptic vesicle exocytosis and endocytic retrieval at the Drosophila neuromuscular junction.
Kuromi, H., Ueno, K. & Kidokoro, Y. Two types of Ca2+ channel linked to two endocytic pathways coordinately maintain synaptic transmission at the Drosophila synapse. Eur. J. Neurosci. 32, 335–346 (2010).
Yamashita, T., Eguchi, K., Saitoh, N., von Gersdorff, H. & Takahashi, T. Developmental shift to a mechanism of synaptic vesicle endocytosis requiring nanodomain Ca2+. Nature Neurosci. 13, 838–844 (2010).
Igarashi, M. & Watanabe, M. Roles of calmodulin and calmodulin-binding proteins in synaptic vesicle recycling during regulated exocytosis at submicromolar Ca2+ concentrations. Neurosci. Res. 58, 226–233 (2007).
Wu, X. S. et al. Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal. Nature Neurosci. 12, 1003–1010 (2009).
Sakaba, T. & Neher, E. Calmodulin mediates rapid recruitment of fast-releasing synaptic vesicles at a calyx-type synapse. Neuron 32, 1119–1131 (2001).
Anggono, V. et al. Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nature Neurosci. 9, 752–760 (2006).
Kuromi, H., Yoshihara, M. & Kidokoro, Y. An inhibitory role of calcineurin in endocytosis of synaptic vesicles at nerve terminals of Drosophila larvae. Neurosci. Res. 27, 101–113 (1997).
Rizo, J. & Rosenmund, C. Synaptic vesicle fusion. Nature Struct. Mol. Biol. 15, 665–674 (2008).
Augustine, G. J., Santamaria, F. & Tanaka, K. Local calcium signaling in neurons. Neuron 40, 331–346 (2003).
Fouquet, W. et al. Maturation of active zone assembly by Drosophila Bruchpilot. J. Cell Biol. 186, 129–145 (2009).
Mukherjee, K. et al. Piccolo and bassoon maintain synaptic vesicle clustering without directly participating in vesicle exocytosis. Proc. Natl Acad. Sci. USA 107, 6504–6509 (2010).
Siksou, L. et al. A common molecular basis for membrane docking and functional priming of synaptic vesicles. Eur. J. Neurosci. 30, 49–56 (2009).
Fernandez-Busnadiego, R. et al. Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography. J. Cell Biol. 188, 145–156 (2010). References 105 and 106 provide ultrastructural evidence for the existence of tethers connecting synaptic vesicles to the active zone.
Hallermann, S. et al. Naked Dense Bodies Provoke Depression. J. Neurosci. 30, 14340–14345 (2010).
Bai, J., Hu, Z., Dittman, J. S., Pym, E. C. & Kaplan, J. M. Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell 143, 430–441 (2010).
Jin, Y. & Garner, C. C. Molecular Mechanisms of Presynaptic Differentiation. Annu. Rev. Cell Dev. Biol. 24, 237–262 (2008).
Owald, D. & Sigrist, S. J. Assembling the presynaptic active zone. Curr. Opin. Neurobiol. 19, 311–318 (2009).
Schoch, S. & Gundelfinger, E. D. Molecular organization of the presynaptic active zone. Cell Tissue Res. 326, 379–391 (2006).
Tsuriel, S. et al. Exchange and redistribution dynamics of the cytoskeleton of the active zone molecule bassoon. J. Neurosci. 29, 351–358 (2009).
Meinrenken, C. J., Borst, J. G. & Sakmann, B. Calcium secretion coupling at calyx of held governed by nonuniform channel-vesicle topography. J. Neurosci. 22, 1648–1667 (2002).
Horn, R. & Marty, A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J. Gen. Physiol. 92, 145–159 (1988).
Rizzoli, S. O., Richards, D. A. & Betz, W. J. Monitoring synaptic vesicle recycling in frog motor nerve terminals with FM dyes. J. Neurocytol. 32, 539–549 (2003).
Zhang, Q., Li, Y. & Tsien, R. W. The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles. Science 323, 1448–1453 (2009).
Royle, S. J., Granseth, B., Odermatt, B., Derevier, A. & Lagnado, L. Imaging phluorin-based probes at hippocampal synapses. Methods Mol. Biol. 457, 293–303 (2008).
Schneggenburger, R. & Neher, E. Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406, 889–893 (2000).
Hell, S. W. Far-field optical nanoscopy. Science 316, 1153–1158 (2007).
Acknowledgements
Work in the authors' laboratories was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft; DFG).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Related links
Related links
FURTHER INFORMATION
Glossary
- Active zone
-
(Often abbreviated to AZ.) An area in the presynaptic compartment that is specialized for rapid exocytosis and contains multidomain proteins acting as scaffolds in the organization of release sites.
- Periactive zone
-
An array of endocytic proteins that surround the active zone and into which synaptic vesicle membranes are recycled following exocytosis.
- Release site
-
Docking sites for synaptic vesicles within active zones that can be empty and accessible for a vesicle, occupied and ready for fusion, or empty and inaccessible.
- Cytoplasmic matrix of the active zone
-
(Often abbreviated to CAZ.) An electron-dense largely detergent-resistant matrix comprising multidomain proteins that may form release sites for exocytosis.
- Super-resolution light microscopic techniques
-
Forms of light microscopic technique that achieve spatial resolution of 50 to 100 nm, beyond the limit set by diffraction; they include stimulated emission depletion microscopy (STED), photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM).
Rights and permissions
About this article
Cite this article
Haucke, V., Neher, E. & Sigrist, S. Protein scaffolds in the coupling of synaptic exocytosis and endocytosis. Nat Rev Neurosci 12, 127–138 (2011). https://doi.org/10.1038/nrn2948
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrn2948
This article is cited by
-
Large-scale simulation of biomembranes incorporating realistic kinetics into coarse-grained models
Nature Communications (2020)
-
A minimalist model to measure interactions between proteins and synaptic vesicles
Scientific Reports (2020)
-
Effect of Transmembrane Electric Field on GM1 Containing DMPC–Cholesterol Monolayer: A Computational Study
The Journal of Membrane Biology (2020)
-
Dendritic spine morphology and memory formation depend on postsynaptic Caskin proteins
Scientific Reports (2019)
-
Antibody-driven capture of synaptic vesicle proteins on the plasma membrane enables the analysis of their interactions with other synaptic proteins
Scientific Reports (2019)