CoChat
Sign Up
Cited by 97Cellular transport and secretionNeuroscience and Neuropharmacology ResearchCalcium signaling and nucleotide metabolism

Developmental shift to a mechanism of synaptic vesicle endocytosis requiring nanodomain Ca2+

Open access
Yamashita, Takayuki, Eguchi, Kohgaku, Saitoh, Naoto, von Gersdorff, Henrique, Takahashi, Tomoyuki·2010·Nature Neuroscience
DOI 10.1038/nn.2576PMC PMC3677945
Open this paper in CoChat — free account

Abstract

Ca(2+) is thought to be essential for the exocytosis and endocytosis of synaptic vesicles. However, the manner in which Ca(2+) coordinates these processes remains unclear, particularly at mature synapses. Using membrane capacitance measurements from calyx of Held nerve terminals in rats, we found that vesicle endocytosis is initiated primarily in Ca(2+) nanodomains around Ca(2+) channels, where exocytosis is triggered. Bulk Ca(2+) outside of the domain could also be involved in endocytosis at immature synapses, although only after extensive exocytosis at more mature synapses. This bulk Ca(2+)-dependent endocytosis required calmodulin and calcineurin activation at immature synapses, but not at more mature synapses. Similarly, GTP-independent endocytosis, which occurred after extensive exocytosis at immature synapses, became negligible after maturation. We propose that nanodomain Ca(2+) simultaneously triggers exocytosis and endocytosis of synaptic vesicles and that the molecular mechanisms underlying Ca(2+)-dependent endocytosis undergo major developmental changes at this fast central synapse.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nn.2576

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Several previous studies suggest that endocytosis becomes slower when neurons are treated with the high-affinity calcium chelator EGTA, which abolishes asynchronous release.

    “Consistent with this notion, several previous studies suggest that endocytosis becomes slower when neurons are treated with the high-affinity calcium chelator EGTA, which abolishes asynchronous release77–81.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [78]

    The Results (Effects of Ca2+ buffers on vesicle endocytosis; page unavailable) report that EGTA slowed endocytosis at immature rat calyces, though it had no effect after a short pulse at more mature calyces. The paper says EGTA strongly reduces transmitter release at immature calyces, but does not say it abolishes asynchronous release. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 46

  1. [1]Heuser JE Reese TS Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction J Cell Biol 57 315 344 1973 4348786 PMC2108984
  2. [2]Koenig JH Ikeda K Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval J Neurosci 9 3844 3860 1989 2573698 PMC6569944
  3. [3]Artalejo CR Henley JR McNiven MA Palfrey HC Rapid endocytosis coupled to exocytosis in adrenal chromaffin cells involves Ca2+, GTP and dynamin, but not clathrin Proc Natl Acad Sci USA 92 8328 8332 1995 7667289 PMC41150
  4. [4]Neves G Gomis A Lagnado L Calcium influx selects the fast mode of endocytosis in the synaptic terminal of retinal bipolar cells Proc Natl Acad Sci USA 98 15282 15287 2001 11734626 PMC65021
  5. [5]Beutner D Voets T Neher E Moser T Calcium dependence of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse Neuron 29 681 690 2001 11301027
  6. [6]Wu W Xu J Wu X-S Wu L-G Activity-dependent acceleration of endocytosis at a central synapse J Neurosci 25 11676 11683 2005 16354926 PMC1378116
  7. [7]Hosoi N Holt M Sakaba T Calcium-dependence of exo- and endocytotic coupling at a glutamatergic synapse Neuron 63 216 229 2009 19640480
  8. [8]Wu X-S Ca2+ and calmodulin initiates all forms of endocytosis during depolarization at a nerve terminal Nat Neurosci 12 1003 1010 2009 19633667 PMC4887276
  9. [9]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 17942618
  10. [10]Granseth B Odermatt B Royle SJ Lagnado L Clathrin-mediated endocytosis is the dominant mechanism of vesicle retrieval at hippocampal synapses Neuron 51 773 786 2006 16982422
  11. [11]Balaji J Armbruster M Ryan TA Calcium control of endocytic capacity at a CNS synapse J Neurosci 28 6742 6749 2008 18579748 PMC2671224
  12. [12]Naraghi M Neher E Linearized buffered Ca2+ diffusion in microdomains and its implications for calculation of [Ca2+] at the mouth of a calcium channel J Neurosci 17 6961 6973 1997 9278532 PMC6573285
  13. [13]Augustine GJ Santamaria F Tanaka K Local calcium signaling in neurons Neuron 40 331 346 2003 14556712
  14. [14]Jewett DL Romano MN Neonatal development of auditory system potentials averaged from the scalp of rat and cat Brain Res 36 101 115 1972 5008374
  15. [15]Borst JGG Sakmann B Calcium influx and transmitter release in a fast CNS synapse Nature 383 431 434 1996 8837774
  16. [16]Fedchyshyn MJ Wang L-Y Developmental transformation of the release modality at the calyx of Held synapse J Neurosci 25 4131 4140 2005 15843616 PMC6724960
  17. [17]Artalejo CR Elhamdani A Palfrey HC Calmodulin is the divalent cation receptor for rapid endocytosis, but not exocytosis, in adrenal chromaffin cells Neuron 16 195 205 1996 8562084
  18. [18]Engisch KL Nowycky MC Compensatory and excess retrieval: two types of endocytosis following single step depolarizations in bovine adrenal chromaffin cells J Physiol (Lond) 506 591 608 1998 9503324 PMC2230744
  19. [19]Chan S-A Smith C Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells J Physiol (Lond) 537 871 885 2001 11744761 PMC2279013
  20. [20]Marks B McMahon HT Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals Curr Biol 8 740 749 1998 9651678
  21. [21]Cousin MA Robinson PJ The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis Trends Neurosci 24 659 665 2001 11672811
  22. [22]Slepnev VI Ochoa G-C Butler MH Grabs D De Camilli P Role of phosphorylation in regulation of the assembly of endocytic coat complexes Science 281 821 824 1998 9694653
  23. [23]Yamashita T Hige T Takahashi T Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse Science 307 124 127 2005 15637282
  24. [24]Jockusch WJ Praefcke GJK McMahon HT Lagnado L Clathrin-dependent and clathrin-independent retrieval of synaptic vesicles in retinal bipolar cells Neuron 46 869 878 2005 15953416
  25. [25]Heidelberger R ATP is required at an early step in compensatory endocytosis in synaptic terminals J Neurosci 21 6467 6474 2001 11517235 PMC6763084
  26. [26]Xu J GTP-independent rapid and slow endocytosis at a central synapse Nat Neurosci 11 45 53 2008 18066059
  27. [27]Török K Inhibition of calmodulin-activated smooth-muscle myosin light-chain kinase by calmodulin-binding peptides and fluorescent (phosphodiesterase-activating) calmodulin derivatives Biochemistry 37 6188 6198 1998 9558358
  28. [28]Nakamura T Yamashita T Saitoh N Takahashi T Developmental changes in calcium/calmodulin-dependent inactivation of calcium currents at the rat calyx of Held J Physiol (Lond) 586 2253 2261 2008 18238813 PMC2479563
  29. [29]Neher E Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release Neuron 20 389 399 1998 9539117
  30. [30]Gad H Löw 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 9768846
  31. [31]Roos J Kelly RB The endocytic machinery in nerve terminals surrounds sites of exocytosis Curr Biol 9 1411 1414 1999 10607569
  32. [32]Teng H Wilkinson RS Clathrin-mediated endocytosis near active zones in snake motor boutons J Neurosci 20 7986 7993 2000 11050119 PMC6772710
  33. [33]Poskanzer KE Marek KW Sweeney ST Davis GW Synaptotagmin 1 is necessary for compensatory synaptic vesicle endocytosis in vivo Nature 426 559 563 2003 14634669
  34. [34]Llinás RR Sugimori M Moran KA Moreira JE Fukuda M Vesicular reuptake inhibition by a synaptotagmin I C2B domain antibody at the squid giant synapse Proc Natl Acad Sci USA 101 17855 17860 2004 15591349 PMC539760
  35. [35]Daly C Ziff EB Ca2+-dependent formation of a dynamin-synaptophysin complex: potential role in synaptic vesicle endocytosis J Biol Chem 277 9010 9015 2002 11779869
  36. [36]Chen Y Formation of an endophillin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis Cell 115 37 48 2003 14532001
  37. [37]Watanabe H Involvement of Ca2+ channel synprint site in synaptic vesicle endocytosis J Neurosci 30 655 660 2010 20071530 PMC6632990
  38. [38]Xu J Wu L-G The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse Neuron 46 633 645 2005 15944131
  39. [41]Burgoyne RD Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signaling Nat Rev Neurosci 8 182 193 2007 17311005 PMC1887812
  40. [42]Kawasaki F Hazen M Ordway RW Fast synaptic fatigue in shibire mutants reveals a rapid requirement for dynamin in synaptic membrane trafficking Nat Neurosci 3 859 860 2000 10966613
  41. [43]Wu Y Kawasaki F Ordway RW Properties of short-term synaptic depression at larval neuromuscular synapses in wild-type and temperature-sensitive paralytic mutants of Drosophila J Neurophysiol 93 2396 2405 2005 15845998
  42. [44]Lou X Paradise S Ferguson SM De Camilli P Selective saturation of slow endocytosis at a giant glutamatergic central synapse lacking dynamin 1 Proc Natl Acad Sci USA 105 17555 17560 2008 18987309 PMC2579887
  43. [45]Newton AJ Kirchhausen T Murthy VN Inhibition of dynamin completely blocks compensatory synaptic vesicle endocytosis Proc Natl Acad Sci USA 103 17955 17960 2006 17093049 PMC1693854
  44. [46]von Gersdorff H Matthews G Inhibition of endocytosis by elevated internal calcium in a synaptic terminal Nature 370 652 655 1994 8065451
  45. [47]Wu L-G Ryan TA Lagnado L Modes of vesicle retrieval at ribbon synapses, calyx-type synapses and small central synapses J Neurosci 27 11793 11802 2007 17978015 PMC6673382
  46. [48]Kimura M Saitoh N Takahashi T Adenosine A1 receptor–mediated presynaptic inhibition at the calyx of Held of immature rats J Physiol (Lond) 553 415 426 2003 12963795 PMC2343556

Cited by

Sorted by citations

Authors
Yamashita, T., Eguchi, K., Saitoh, N., von Gersdorff, H., & Takahashi, T.
Affiliations
  • Okinawa Institute of Science and Technology Graduate University (JP)
  • Doshisha University (JP)
Corresponding author
  • Yamashita, Takayuki
  • Takahashi, Tomoyuki
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2010-06-20
Volume
13
Issue
7
Pages
838-844
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.2576
PMC
PMC3677945
OpenAlex
W2044167411
Cited by
97
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 10 · 2023: 7 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 7 · 2012: 7
FWCI
3.50
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Japan Science Society
  • National Institutes of Health
  • Japan Science and Technology Agency
  • National Eye Institute (EY014043, R01EY014043)
  • Core Research for Evolutional Science and Technology
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 › Physiology › Calcium signaling and nucleotide metabolism
Keywords
synaptic vesicle endocytosis, calcium nanodomains, calyx of Held, synapse maturation, exocytosis, calmodulin, calcineurin, GTP hydrolysis, calcium channels, hearing onset, membrane capacitance
MeSH terms
Animals, Auditory Pathways, Brain Stem, Calcium, Calmodulin, Endocytosis, Exocytosis, Synaptic Vesicles, Time Factors, Signal Transduction, Rats, Wistar, Calcineurin, Membrane Microdomains, Electric Capacitance, Rats, Neurogenesis, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review