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Cited by 78Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Optical detection of three modes of endocytosis at hippocampal synapses

Open access
Chanaday, Natali L, Kavalali, Ege T·2018·eLife
DOI 10.7554/elife.36097PMC PMC5959719
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Abstract

Coupling of synaptic vesicle fusion and retrieval constitutes a core mechanism ensuring maintenance of presynaptic function. Recent studies using fast-freeze electron microscopy and capacitance measurements reported an ultrafast mode of endocytosis operating at physiological temperatures. Here, using rat hippocampal neurons, we optically monitored single synaptic vesicle endocytosis with high time resolution using the vesicular glutamate transporter, synaptophysin and the V0a1 subunit of the vacuolar ATPase as probes. In this setting, we could distinguish three components of retrieval operating at ultrafast (~150–250 ms, ~20% of events), fast (~5–12 s, ~40% of events) and ultraslow speeds (>20 s, ~40% of events). While increasing Ca2+ slowed the fast events, increasing temperature accelerated their time course. In contrast, the kinetics of ultrafast events were only mildly affected by these manipulations. These results suggest that synaptic vesicle proteins can be retrieved with ultrafast kinetics, although a majority of evoked fusion events are coupled to slower retrieval mechanisms.

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  • When ultrafast endocytosis is blocked, a slow clathrin-mediated endocytic pathway can kick in.

    “When ultrafast endocytosis is blocked, a slow clathrin-mediated endocytic pathway can kick in7 - this is consistent with observations from live-cell imaging of endocytosis68–70.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [70]

    The Discussion reports slow retrieval alongside ultrafast retrieval and says the ultraslow mode could be compatible with a process mediated by clathrin adaptors. It describes the pathways as operating in parallel, however, and does not show that blocking ultrafast endocytosis causes a slow clathrin-mediated pathway to take over. (LLM, conf=0.84)

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Research works printed but not linked: 50

  1. Alabi AA Tsien RW 2013 Perspectives on kiss-and-run: role in exocytosis, endocytosis, and neurotransmission Annual Review of Physiology 75 393 422 10.1146/annurev-physiol-020911-153305 23245563 · DOI
  2. Bagh MB Peng S Chandra G Zhang Z Singh SP Pattabiraman N Liu A Mukherjee AB 2017 Misrouting of v-ATPase subunit V0a1 dysregulates lysosomal acidification in a neurodegenerative lysosomal storage disease model Nature Communications 8 14612 10.1038/ncomms14612 28266544 PMC5344305 · DOI
  3. Bennett MK Calakos N Kreiner T Scheller RH 1992 Synaptic vesicle membrane proteins interact to form a multimeric complex The Journal of Cell Biology 116 761 775 10.1083/jcb.116.3.761 1730776 PMC2289316 · DOI
  4. Chanaday NL Kavalali ET 2017 How do you recognize and reconstitute a synaptic vesicle after fusion? F1000Research 6 1734 10.12688/f1000research.12072.1 29034086 PMC5615776 · DOI
  5. Chung C Kavalali ET 2009 Synaptic vesicle endocytosis: get two for the price of one? Neuron 61 333 334 10.1016/j.neuron.2009.01.022 19217369 · DOI
  6. Chung SH Kennedy RA 1991 Forward-backward non-linear filtering technique for extracting small biological signals from noise Journal of Neuroscience Methods 40 71 86 10.1016/0165-0270(91)90118-J 1795554 · DOI
  7. Crawford DC Kavalali ET 2015 Molecular underpinnings of synaptic vesicle pool heterogeneity Traffic 16 338 364 10.1111/tra.12262 25620674 PMC4578802 · DOI
  8. Deák F Shin OH Kavalali ET Südhof TC 2006 Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion Journal of Neuroscience 26 6668 6676 10.1523/JNEUROSCI.5272-05.2006 16793874 PMC6673840 · DOI
  9. Delvendahl I Vyleta NP von Gersdorff H Hallermann S 2016 Fast, temperature-sensitive and clathrin-independent endocytosis at central synapses Neuron 90 492 498 10.1016/j.neuron.2016.03.013 27146271 PMC5125781 · DOI · Paper page
  10. Fernández-Alfonso T Ryan TA 2004 The kinetics of synaptic vesicle pool depletion at CNS synaptic terminals Neuron 41 943 953 10.1016/S0896-6273(04)00113-8 15046726 · DOI
  11. Gandhi SP Stevens CF 2003 Three modes of synaptic vesicular recycling revealed by single-vesicle imaging Nature 423 607 613 10.1038/nature01677 12789331 · DOI
  12. Gimber N Tadeus G Maritzen T Schmoranzer J Haucke V 2015 Diffusional spread and confinement of newly exocytosed synaptic vesicle proteins Nature Communications 6 8392 10.1038/ncomms9392 26399746 PMC4598626 · DOI
  13. 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 10.1016/j.neuron.2006.08.029 16982422 · DOI
  14. He L Wu XS Mohan R Wu LG 2006 Two modes of fusion pore opening revealed by cell-attached recordings at a synapse Nature 444 102 105 10.1038/nature05250 17065984 · DOI
  15. Hua Y Woehler A Kahms M Haucke V Neher E Klingauf J 2013 Blocking endocytosis enhances short-term synaptic depression under conditions of normal availability of vesicles Neuron 80 343 349 10.1016/j.neuron.2013.08.010 24139039 · DOI
  16. Kavalali ET Jorgensen EM 2014 Visualizing presynaptic function Nature Neuroscience 17 10 16 10.1038/nn.3578 24369372 · DOI · Paper page
  17. Kavalali ET Klingauf J Tsien RW 1999 Properties of fast endocytosis at hippocampal synapses Philosophical Transactions of the Royal Society B: Biological Sciences 354 337 346 10.1098/rstb.1999.0385 10212482 PMC1692492 · DOI
  18. Kavalali ET 2006 Synaptic vesicle reuse and its implications The Neuroscientist 12 57 66 10.1177/1073858405281852 16394193 · DOI
  19. Klingauf J Kavalali ET Tsien RW 1998 Kinetics and regulation of fast endocytosis at hippocampal synapses Nature 394 581 585 10.1038/29079 9707119 · DOI
  20. Klyachko VA Jackson MB 2002 Capacitance steps and fusion pores of small and large-dense-core vesicles in nerve terminals Nature 418 89 92 10.1038/nature00852 12097912 · DOI
  21. Kushmerick C Renden R von Gersdorff H 2006 Physiological temperatures reduce the rate of vesicle pool depletion and short-term depression via an acceleration of vesicle recruitment Journal of Neuroscience 26 1366 1377 10.1523/JNEUROSCI.3889-05.2006 16452660 PMC6675486 · DOI
  22. Leitz J Kavalali ET 2011 Ca²⁺ influx slows single synaptic vesicle endocytosis Journal of Neuroscience 31 16318 16326 10.1523/JNEUROSCI.3358-11.2011 22072683 PMC3235053 · DOI
  23. Leitz J Kavalali ET 2016 Ca2+ Dependence of Synaptic Vesicle Endocytosis The Neuroscientist 22 464 476 10.1177/1073858415588265 25998187 · DOI
  24. Li Y Tsien RW 2012 pHTomato, a red, genetically encoded indicator that enables multiplex interrogation of synaptic activity Nature Neuroscience 15 1047 1053 10.1038/nn.3126 22634730 PMC3959862 · DOI
  25. Li YC Chanaday NL Xu W Kavalali ET 2017 Synaptotagmin-1- and Synaptotagmin-7-Dependent fusion mechanisms target synaptic vesicles to kinetically distinct endocytic pathways Neuron 93 e613 631 10.1016/j.neuron.2016.12.010 28111077 PMC5300960 · DOI
  26. Miller TM Heuser JE 1984 Endocytosis of synaptic vesicle membrane at the frog neuromuscular junction The Journal of Cell Biology 98 685 698 10.1083/jcb.98.2.685 6607255 PMC2113115 · DOI
  27. Morel N Dedieu JC Philippe JM 2003 Specific sorting of the a1 isoform of the V-H+ATPase a subunit to nerve terminals where it associates with both synaptic vesicles and the presynaptic plasma membrane Journal of Cell Science 116 4751 4762 10.1242/jcs.00791 14600261 · DOI
  28. Mozhayeva MG Sara Y Liu X Kavalali ET 2002 Development of vesicle pools during maturation of hippocampal synapses The Journal of Neuroscience 22 654 665 10.1523/JNEUROSCI.22-03-00654.2002 11826095 PMC6758530 · DOI
  29. Murthy VN Sejnowski TJ Stevens CF 1997 Heterogeneous release properties of visualized individual hippocampal synapses Neuron 18 599 612 10.1016/S0896-6273(00)80301-3 9136769 · DOI
  30. Opazo F Rizzoli SO 2010 The fate of synaptic vesicle components upon fusion Communicative & Integrative Biology 3 427 429 10.4161/cib.3.5.12132 21057631 PMC2974071 · DOI
  31. Pan PY Marrs J Ryan TA 2015 Vesicular glutamate transporter 1 orchestrates recruitment of other synaptic vesicle cargo proteins during synaptic vesicle recycling Journal of Biological Chemistry 290 22593 22601 10.1074/jbc.M115.651711 26224632 PMC4566233 · DOI
  32. Pyott SJ Rosenmund C 2002 The effects of temperature on vesicular supply and release in autaptic cultures of rat and mouse hippocampal neurons The Journal of Physiology 539 523 535 10.1113/jphysiol.2001.013277 11882684 PMC2290147 · DOI
  33. Raingo J Khvotchev M Liu P Darios F Li YC Ramirez DM Adachi M Lemieux P Toth K Davletov B Kavalali ET 2012 VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission Nature Neuroscience 15 738 745 10.1038/nn.3067 22406549 PMC3337975 · DOI
  34. Ramirez DM Andersson S Russell DW 2008 Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain The Journal of Comparative Neurology 507 1676 1693 10.1002/cne.21605 18241055 PMC4015140 · DOI
  35. Renden R von Gersdorff H 2007 Synaptic vesicle endocytosis at a CNS nerve terminal: faster kinetics at physiological temperatures and increased endocytotic capacity during maturation Journal of Neurophysiology 98 3349 3359 10.1152/jn.00898.2007 17942618 · DOI
  36. Reuel NF Bojo P Zhang J Boghossian AA Ahn JH Kim JH Strano MS 2012 NoRSE: noise reduction and state evaluator for high-frequency single event traces Bioinformatics 28 296 297 10.1093/bioinformatics/btr632 22088841 · DOI
  37. Ryan TA Smith SJ Reuter H 1996 The timing of synaptic vesicle endocytosis PNAS 93 5567 5571 10.1073/pnas.93.11.5567 8643616 PMC39287 · DOI
  38. Sara Y Mozhayeva MG Liu X Kavalali ET 2002 Fast vesicle recycling supports neurotransmission during sustained stimulation at hippocampal synapses The Journal of Neuroscience 22 1608 1617 10.1523/JNEUROSCI.22-05-01608.2002 11880491 PMC6758906 · DOI
  39. Schindelin J Arganda-Carreras I Frise E Kaynig V Longair M Pietzsch T Preibisch S Rueden C Saalfeld S Schmid B Tinevez JY White DJ Hartenstein V Eliceiri K Tomancak P Cardona A 2012 Fiji: an open-source platform for biological-image analysis Nature Methods 9 676 682 10.1038/nmeth.2019 22743772 PMC3855844 · DOI · Paper page
  40. Soykan T Kaempf N Sakaba T Vollweiter D Goerdeler F Puchkov D Kononenko NL Haucke V 2017 Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly Neuron 93 e854 866 10.1016/j.neuron.2017.02.011 28231467 · DOI · Paper page
  41. Sun JY Wu XS Wu LG 2002 Single and multiple vesicle fusion induce different rates of endocytosis at a central synapse Nature 417 555 559 10.1038/417555a 12037569 · DOI
  42. Südhof TC 2013 Neurotransmitter release: the last millisecond in the life of a synaptic vesicle Neuron 80 675 690 10.1016/j.neuron.2013.10.022 24183019 PMC3866025 · DOI · Paper page
  43. Van Hook MJ Thoreson WB 2012 Rapid synaptic vesicle endocytosis in cone photoreceptors of salamander retina Journal of Neuroscience 32 18112 18123 10.1523/JNEUROSCI.1764-12.2012 23238726 PMC3547361 · DOI
  44. Voglmaier SM Edwards RH 2007 Do different endocytic pathways make different synaptic vesicles? Current Opinion in Neurobiology 17 374 380 10.1016/j.conb.2007.04.002 17449236 · DOI
  45. Voglmaier SM Kam K Yang H Fortin DL Hua Z Nicoll RA Edwards RH 2006 Distinct endocytic pathways control the rate and extent of synaptic vesicle protein recycling Neuron 51 71 84 10.1016/j.neuron.2006.05.027 16815333 · DOI
  46. von Gersdorff H Matthews G 1994 Dynamics of synaptic vesicle fusion and membrane retrieval in synaptic terminals Nature 367 735 739 10.1038/367735a0 7906397 · DOI
  47. Watanabe S Boucrot E 2017 Fast and ultrafast endocytosis Current Opinion in Cell Biology 47 64 71 10.1016/j.ceb.2017.02.013 28391090 · DOI
  48. Willig KI Rizzoli SO Westphal V Jahn R Hell SW 2006 STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis Nature 440 935 939 10.1038/nature04592 16612384 · DOI
  49. Xu J McNeil B Wu W Nees D Bai L Wu LG 2008 GTP-independent rapid and slow endocytosis at a central synapse Nature Neuroscience 11 45 53 10.1038/nn2021 18066059 · DOI
  50. Zhu Y Xu J Heinemann SF 2009 Two pathways of synaptic vesicle retrieval revealed by single-vesicle imaging Neuron 61 397 411 10.1016/j.neuron.2008.12.024 19217377 PMC2707496 · DOI

Cited by

Sorted by citations

Authors
Chanaday, N. L., & Kavalali, E. T.
Affiliations
  • Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Kavalali, Ege T
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-04-23
Volume
7
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.36097
PMC
PMC5959719
OpenAlex
W2799552138
Cited by
78
References
3
Citations by year
2026: 9 · 2025: 10 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 2
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of Mental Health (MH066198)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
synaptic vesicle endocytosis, synaptic vesicle retrieval, vesicular glutamate transporter, synaptophysin, hippocampal synapses, calcium dependence, temperature dependence, presynaptic function
MeSH terms
Animals, Calcium, Endocytosis, Hippocampus, Synapses, Temperature, Synaptophysin, Vacuolar Proton-Translocating ATPases, Rats, Optical Imaging

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