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Cited by 51Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Synaptotagmin 7 is targeted to the axonal plasma membrane through γ-secretase processing to promote synaptic vesicle docking in mouse hippocampal neurons

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Vevea, Jason D, Kusick, Grant F, Courtney, Kevin C, Chen, Erin, Watanabe, Shigeki, Chapman, Edwin R·2021·eLife
DOI 10.7554/elife.67261PMC PMC8452306

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Abstract

Synaptotagmin 7 (SYT7) has emerged as a key regulator of presynaptic function, but its localization and precise role in the synaptic vesicle cycle remain the subject of debate. Here, we used iGluSnFR to optically interrogate glutamate release, at the single-bouton level, in SYT7KO-dissociated mouse hippocampal neurons. We analyzed asynchronous release, paired-pulse facilitation, and synaptic vesicle replenishment and found that SYT7 contributes to each of these processes to different degrees. ‘Zap-and-freeze’ electron microscopy revealed that a loss of SYT7 diminishes docking of synaptic vesicles after a stimulus and inhibits the recovery of depleted synaptic vesicles after a stimulus train. SYT7 supports these functions from the axonal plasma membrane, where its localization and stability require both γ-secretase-mediated cleavage and palmitoylation. In summary, SYT7 is a peripheral membrane protein that controls multiple modes of synaptic vesicle (SV) exocytosis and plasticity, in part, through enhancing activity-dependent docking of SVs.

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  • Approximately 35% of the total release after a single action potential is contributed by asynchronous release in mouse hippocampal excitatory synapses.

    “Based on previous studies with zap-and-freeze, patch-clamp electrophysiology measurements, and glutamate imaging, ~35% of the total release that occurs after a single action potential is contributed by this asynchronous component in mouse hippocampal excitatory synapses62,66.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [62]

    The Results section on short-term synaptic plasticity reports asynchronous glutamate release after a single stimulus in cultured mouse hippocampal neurons. It reports a small difference between WT and SYT7KO neurons, however, not that asynchronous release accounts for approximately 35% of total release after one action potential. A search for “35%” did not locate that estimate in our copy; no page number is available. (LLM, conf=0.84)

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  • With physiological extracellular calcium (~1 mM), only 1-2 vesicles fuse on average in synapses that respond to a single action potential.

    “However, with a physiological extracellular calcium concentration ( ~1 mM)64, only 1–2 vesicles fuse on average in synapses that respond to a single action potential39,62.”

    From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [62]

    The Results report that release early in a stimulus train was predominantly multiquantal, with an iGluSnFR signal near the paper’s two-quanta estimate. This supports release of roughly two vesicles in that setting, but does not establish an average of 1–2 vesicles per responding synapse after a single action potential. The iGluSnFR imaging methods also specify 2 mM calcium; the sentence cites another source for the ~1 mM condition. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 76

  1. Arantes RM Andrews NW 2006 A role for synaptotagmin VII-regulated exocytosis of lysosomes in neurite outgrowth from primary sympathetic neurons Journal of Neuroscience 26 4630 4637 10.1523/JNEUROSCI.0009-06.2006 16641243 PMC6674075 · DOI
  2. Bacaj T Wu D Yang X Morishita W Zhou P Xu W Malenka RC Südhof TC 2013 Synaptotagmin-1 and synaptotagmin-7 trigger synchronous and asynchronous phases of neurotransmitter release Neuron 80 947 959 10.1016/j.neuron.2013.10.026 24267651 PMC3888870 · DOI
  3. Bajar BT Wang ES Lam AJ Kim BB Jacobs CL Howe ES Davidson MW Lin MZ Chu J 2016 Improving brightness and photostability of green and red fluorescent proteins for live cell imaging and FRET reporting Scientific Reports 6 20889 10.1038/srep20889 26879144 PMC4754705 · DOI
  4. Barrett EF Stevens CF 1972 The kinetics of transmitter release at the frog neuromuscular junction The Journal of Physiology 227 691 708 10.1113/jphysiol.1972.sp010054 4405553 PMC1331282 · DOI
  5. Barthet G Jordà-Siquier T Rumi-Masante J Bernadou F Müller U Mulle C 2018 Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity Nature Communications 9 4780 10.1038/s41467-018-06813-x 30429473 PMC6235831 · DOI
  6. Bhalla A Tucker WC Chapman ER 2005 Synaptotagmin isoforms couple distinct ranges of Ca2+, Ba2+, and Sr2+ concentration to SNARE-mediated membrane fusion Molecular Biology of the Cell 16 4755 4764 10.1091/mbc.e05-04-0277 16093350 PMC1237081 · DOI
  7. Bolte S Cordelières FP 2006 A guided tour into subcellular colocalization analysis in light microscopy Journal of Microscopy 224 213 232 10.1111/j.1365-2818.2006.01706.x 17210054 · DOI
  8. Chakrabarti S Kobayashi KS Flavell RA Marks CB Miyake K Liston DR Fowler KT Gorelick FS Andrews NW 2003 Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice Journal of Cell Biology 162 543 549 10.1083/jcb.200305131 12925704 PMC2173791 · DOI
  9. Chapman ER Blasi J An S Brose N Johnston PA Südhof TC Jahn R 1996 Fatty acylation of synaptotagmin in PC12 cells and synaptosomes Biochemical and Biophysical Research Communications 225 326 332 10.1006/bbrc.1996.1174 8769138 · DOI
  10. Chapman ER 2008 How does synaptotagmin trigger neurotransmitter release? Annual Review of Biochemistry 77 615 641 10.1146/annurev.biochem.77.062005.101135 18275379 · DOI
  11. Chen C Satterfield R Young SM Jonas P 2017 Triple function of synaptotagmin 7 ensures efficiency of High-Frequency transmission at central GABAergic synapses Cell Reports 21 2082 2089 10.1016/j.celrep.2017.10.122 29166601 PMC5863544 · DOI
  12. Cheng XT Xie YX Zhou B Huang N Farfel-Becker T Sheng ZH 2018 Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons Journal of Cell Biology 217 3127 3139 10.1083/jcb.201711083 29695488 PMC6123004 · DOI
  13. Chu BB Liao YC Qi W Xie C Du X Wang J Yang H Miao HH Li BL Song BL 2015 Cholesterol transport through lysosome-peroxisome membrane contacts Cell 161 291 306 10.1016/j.cell.2015.02.019 25860611 · DOI · Paper page
  14. Codner GF Mianné J Caulder A Loeffler J Fell R King R Allan AJ Mackenzie M Pike FJ McCabe CV Christou S Joynson S Hutchison M Stewart ME Kumar S Simon MM Agius L Anstee QM Volynski KE Kullmann DM Wells S Teboul L 2018 Application of long single-stranded DNA donors in genome editing: generation and validation of mouse mutants BMC Biology 16 70 10.1186/s12915-018-0530-7 29925374 PMC6011369 · DOI
  15. Dörrbaum AR Kochen L Langer JD Schuman EM 2018 Local and global influences on protein turnover in neurons and Glia eLife 7 e34202 10.7554/eLife.34202 29914620 PMC6008053 · DOI · Paper page
  16. Dovey HF John V Anderson JP Chen LZ de Saint Andrieu P Fang LY Freedman SB Folmer B Goldbach E Holsztynska EJ Hu KL Johnson-Wood KL Kennedy SL Kholodenko D Knops JE Latimer LH Lee M Liao Z Lieberburg IM Motter RN Mutter LC Nietz J Quinn KP Sacchi KL Seubert PA Shopp GM Thorsett ED Tung JS Wu J Yang S Yin CT Schenk DB May PC Altstiel LD Bender MH Boggs LN Britton TC Clemens JC Czilli DL Dieckman-McGinty DK Droste JJ Fuson KS Gitter BD Hyslop PA Johnstone EM Li WY Little SP Mabry TE Miller FD Audia JE 2001 Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain Journal of Neurochemistry 76 173 181 10.1046/j.1471-4159.2001.00012.x 11145990 · DOI
  17. Flannery AR Czibener C Andrews NW 2010 Palmitoylation-dependent association with CD63 targets the Ca2+ sensor synaptotagmin VII to lysosomes Journal of Cell Biology 191 599 613 10.1083/jcb.201003021 21041449 PMC3003310 · DOI
  18. Fukuda M Ogata Y Saegusa C Kanno E Mikoshiba K 2002 Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human Biochemical Journal 365 173 180 10.1042/bj20011877 12071850 PMC1222667 · DOI
  19. Fukuda M Kanno E Satoh M Saegusa C Yamamoto A 2004 Synaptotagmin VII is targeted to dense-core vesicles and regulates their Ca2+ -dependent exocytosis in PC12 cells Journal of Biological Chemistry 279 52677 52684 10.1074/jbc.M409241200 15456748 · DOI
  20. Gauthier BR Duhamel DL Iezzi M Theander S Saltel F Fukuda M Wehrle-Haller B Wollheim CB 2008 Synaptotagmin VII splice variants alpha, beta, and delta are expressed in pancreatic beta-cells and regulate insulin exocytosis The FASEB Journal 22 194 206 10.1096/fj.07-8333com 17709608 · DOI
  21. Grimm JB Muthusamy AK Liang Y Brown TA Lemon WC Patel R Lu R Macklin JJ Keller PJ Ji N Lavis LD 2017 A general method to fine-tune fluorophores for live-cell and in vivo imaging Nature Methods 14 987 994 10.1038/nmeth.4403 28869757 PMC5621985 · DOI
  22. Gustavsson N Lao Y Maximov A Chuang JC Kostromina E Repa JJ Li C Radda GK Südhof TC Han W 2008 Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice PNAS 105 3992 3997 10.1073/pnas.0711700105 18308938 PMC2268794 · DOI
  23. Hui E Bai J Wang P Sugimori M Llinas RR Chapman ER 2005 Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis PNAS 102 5210 5214 10.1073/pnas.0500941102 15793006 PMC556003 · DOI
  24. Huson V Regehr WG 2020 Diverse roles of Synaptotagmin-7 in regulating vesicle fusion Current Opinion in Neurobiology 63 42 52 10.1016/j.conb.2020.02.006 32278209 PMC10305731 · DOI
  25. Jackman SL Turecek J Belinsky JE Regehr WG 2016 The calcium sensor synaptotagmin 7 is required for synaptic facilitation Nature 529 88 91 10.1038/nature16507 26738595 PMC4729191 · DOI
  26. Katz B Miledi R 1965 The effect of calcium on acetylcholine release from motor nerve terminals Proceedings of the Royal Society of London. Series B, Biological Sciences 161 496 503 10.1098/rspb.1965.0017 14278410 · DOI
  27. Kopan R Ilagan MX 2004 Gamma-secretase: proteasome of the membrane? Nature Reviews Molecular Cell Biology 5 499 504 10.1038/nrm1406 15173829 · DOI
  28. Kügler S Kilic E Bähr M 2003 Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area Gene Therapy 10 337 347 10.1038/sj.gt.3301905 12595892 · DOI
  29. Kusick GF Chin M Raychaudhuri S Lippmann K Adula KP Hujber EJ Vu T Davis MW Jorgensen EM Watanabe S 2020 Synaptic vesicles transiently dock to refill release sites Nature Neuroscience 23 1329 1338 10.1038/s41593-020-00716-1 32989294 PMC8054220 · DOI · Paper page
  30. Lau PM Bi GQ 2005 Synaptic mechanisms of persistent reverberatory activity in neuronal networks PNAS 102 10333 10338 10.1073/pnas.0500717102 16006530 PMC1177363 · DOI
  31. Li C Ullrich B Zhang JZ Anderson RG Brose N Südhof TC 1995 Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins Nature 375 594 599 10.1038/375594a0 7791877 · DOI · Paper page
  32. Li Y Wang P Xu J Gorelick F Yamazaki H Andrews N Desir GV 2007 Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII Biochemical and Biophysical Research Communications 362 658 664 10.1016/j.bbrc.2007.08.023 17720139 PMC2194288 · DOI
  33. Littleton JT Stern M Schulze K Perin M Bellen HJ 1993 Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release Cell 74 1125 1134 10.1016/0092-8674(93)90733-7 8104705 · DOI
  34. Liu H Bai H Hui E Yang L Evans CS Wang Z Kwon SE Chapman ER 2014a Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment eLife 3 e01524 10.7554/eLife.01524 24569478 PMC3930910 · DOI
  35. Liu H Bai H Xue R Takahashi H Edwardson JM Chapman ER 2014b Linker mutations reveal the complexity of synaptotagmin 1 action during synaptic transmission Nature Neuroscience 17 670 677 10.1038/nn.3681 24657966 PMC4139111 · DOI
  36. Lois C Hong EJ Pease S Brown EJ Baltimore D 2002 Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors Science 295 868 872 10.1126/science.1067081 11786607 · DOI
  37. Martinez I Chakrabarti S Hellevik T Morehead J Fowler K Andrews NW 2000 Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts Journal of Cell Biology 148 1141 1150 10.1083/jcb.148.6.1141 10725327 PMC2174306 · DOI
  38. Marvin JS Scholl B Wilson DE Podgorski K Kazemipour A Müller JA Schoch S Quiroz FJU Rebola N Bao H Little JP Tkachuk AN Cai E Hantman AW Wang SS DePiero VJ Borghuis BG Chapman ER Dietrich D DiGregorio DA Fitzpatrick D Looger LL 2018 Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR Nature Methods 15 936 939 10.1038/s41592-018-0171-3 30377363 PMC6394230 · DOI
  39. Matsuda T Cepko CL 2004 Electroporation and RNA interference in the rodent retina in vivo and in vitro PNAS 101 16 22 10.1073/pnas.2235688100 14603031 PMC314130 · DOI
  40. Maximov A Lao Y Li H Chen X Rizo J Sørensen JB Südhof TC 2008 Genetic analysis of synaptotagmin-7 function in synaptic vesicle exocytosis PNAS 105 3986 3991 10.1073/pnas.0712372105 18308933 PMC2268828 · DOI
  41. McGuinness L Bardo SJ Emptage NJ 2007 The lysosome or lysosome-related organelle may serve as a Ca2+ store in the boutons of hippocampal pyramidal cells Neuropharmacology 52 126 135 10.1016/j.neuropharm.2006.07.029 16930634 · DOI
  42. Mitter D Reisinger C Hinz B Hollmann S Yelamanchili SV Treiber-Held S Ohm TG Herrmann A Ahnert-Hilger G 2003 The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content Journal of Neurochemistry 84 35 42 10.1046/j.1471-4159.2003.01258.x 12485399 · DOI
  43. Monterrat C Grise F Benassy MN Hémar A Lang J 2007 The calcium-sensing protein synaptotagmin 7 is expressed on different endosomal compartments in endocrine, neuroendocrine cells or neurons but not on large dense core vesicles Histochemistry and Cell Biology 127 625 632 10.1007/s00418-007-0271-0 17277932 · DOI
  44. Nishiki T Augustine GJ 2004 Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons Journal of Neuroscience 24 6127 6132 10.1523/JNEUROSCI.1563-04.2004 15240804 PMC6729667 · DOI
  45. Padamsey Z McGuinness L Bardo SJ Reinhart M Tong R Hedegaard A Hart ML Emptage NJ 2017 Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines Neuron 93 132 146 10.1016/j.neuron.2016.11.013 27989455 PMC5222721 · DOI · Paper page
  46. Pang ZP Melicoff E Padgett D Liu Y Teich AF Dickey BF Lin W Adachi R Südhof TC 2006 Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses Journal of Neuroscience 26 13493 13504 10.1523/JNEUROSCI.3519-06.2006 17192432 PMC6674714 · DOI
  47. Parmar HB Barry C Kai F Duncan R 2014 Golgi complex-plasma membrane trafficking directed by an autonomous, tribasic Golgi export signal Molecular Biology of the Cell 25 866 878 10.1091/mbc.e13-07-0364 24451258 PMC3952855 · DOI
  48. Rao TC Passmore DR Peleman AR Das M Chapman ER Anantharam A 2014 Distinct fusion properties of synaptotagmin-1 and synaptotagmin-7 bearing dense core granules Molecular Biology of the Cell 25 2416 2427 10.1091/mbc.e14-02-0702 24943843 PMC4142614 · DOI
  49. Reddy A Caler EV Andrews NW 2001 Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes Cell 106 157 169 10.1016/S0092-8674(01)00421-4 11511344 · DOI
  50. Sakurai K Zhao S Takatoh J Rodriguez E Lu J Leavitt AD Fu M Han BX Wang F 2016 Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit Neuron 92 739 753 10.1016/j.neuron.2016.10.015 27974160 PMC5172402 · DOI
  51. 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
  52. Schonn JS Maximov A Lao Y Südhof TC Sørensen JB 2008 Synaptotagmin-1 and -7 are functionally overlapping Ca2+ sensors for exocytosis in adrenal chromaffin cells PNAS 105 3998 4003 10.1073/pnas.0712373105 18308932 PMC2268838 · DOI
  53. Shen W Wang QW Liu YN Marchetto MC Linker S Lu SY Chen Y Liu C Guo C Xing Z Shi W Kelsoe JR Alda M Wang H Zhong Y Sui SF Zhao M Yang Y Mi S Cao L Gage FH Yao J 2020 Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice PNAS 117 4392 4399 10.1073/pnas.1918165117 32041882 PMC7049155 · DOI
  54. Südhof TC 2002 Synaptotagmins: why so many? Journal of Biological Chemistry 277 7629 7632 10.1074/jbc.R100052200 11739399 · DOI
  55. Sugita S Han W Butz S Liu X Fernández-Chacón R Lao Y Südhof TC 2001 Synaptotagmin VII as a plasma membrane Ca(2+) sensor in exocytosis Neuron 30 459 473 10.1016/S0896-6273(01)00290-2 11395007 · DOI
  56. Suzuki K Tsunekawa Y Hernandez-Benitez R Wu J Zhu J Kim EJ Hatanaka F Yamamoto M Araoka T Li Z Kurita M Hishida T Li M Aizawa E Guo S Chen S Goebl A Soligalla RD Qu J Jiang T Fu X Jafari M Esteban CR Berggren WT Lajara J Nuñez-Delicado E Guillen P Campistol JM Matsuzaki F Liu GH Magistretti P Zhang K Callaway EM Zhang K Belmonte JC 2016 In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration Nature 540 144 149 10.1038/nature20565 27851729 PMC5331785 · DOI · Paper page
  57. Thiele C Hannah MJ Fahrenholz F Huttner WB 2000 Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles Nature Cell Biology 2 42 49 10.1038/71366 10620806 · DOI
  58. Tokunaga M Imamoto N Sakata-Sogawa K 2008 Highly inclined thin illumination enables clear single-molecule imaging in cells Nature Methods 5 159 161 10.1038/nmeth1171 18176568 · DOI
  59. Turecek J Jackman SL Regehr WG 2017 Synaptotagmin 7 confers frequency invariance onto specialized depressing synapses Nature 551 503 506 10.1038/nature24474 29088700 PMC5892411 · DOI
  60. Turecek J Regehr WG 2018 Synaptotagmin 7 Mediates Both Facilitation and Asynchronous Release at Granule Cell Synapses The Journal of Neuroscience 38 3240 3251 10.1523/JNEUROSCI.3207-17.2018 29593071 PMC5884459 · DOI
  61. Vevea JD Garcia EJ Chan RB Zhou B Schultz M Di Paolo G McCaffery JM Pon LA 2015 Role for Lipid Droplet Biogenesis and Microlipophagy in Adaptation to Lipid Imbalance in Yeast Developmental Cell 35 584 599 10.1016/j.devcel.2015.11.010 26651293 PMC4679156 · DOI
  62. Vevea JD Chapman ER 2020 Acute disruption of the synaptic vesicle membrane protein synaptotagmin 1 using knockoff in mouse hippocampal neurons eLife 9 e56469 10.7554/eLife.56469 32515733 PMC7282819 · DOI
  63. Virmani T Han W Liu X Südhof TC Kavalali ET 2003 Synaptotagmin 7 splice variants differentially regulate synaptic vesicle recycling The EMBO Journal 22 5347 5357 10.1093/emboj/cdg514 14532108 PMC213769 · DOI
  64. Wang P Chicka MC Bhalla A Richards DA Chapman ER 2005 Synaptotagmin VII is targeted to secretory organelles in PC12 cells, where it functions as a high-affinity calcium sensor Molecular and Cellular Biology 25 8693 8702 10.1128/MCB.25.19.8693-8702.2005 16166648 PMC1265757 · DOI
  65. Webb Y Hermida-Matsumoto L Resh MD 2000 Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids Journal of Biological Chemistry 275 261 270 10.1074/jbc.275.1.261 10617614 · DOI
  66. Weber JP Toft-Bertelsen TL Mohrmann R Delgado-Martinez I Sørensen JB 2014 Synaptotagmin-7 is an asynchronous calcium sensor for synaptic transmission in neurons expressing SNAP-23 PLOS ONE 9 e114033 10.1371/journal.pone.0114033 25422940 PMC4244210 · DOI
  67. Weissleder R Tung CH Mahmood U Bogdanov A 1999 In vivo imaging of tumors with protease-activated near-infrared fluorescent probes Nature Biotechnology 17 375 378 10.1038/7933 10207887 · DOI
  68. Wen H Linhoff MW McGinley MJ Li GL Corson GM Mandel G Brehm P 2010 Distinct roles for two synaptotagmin isoforms in synchronous and asynchronous transmitter release at zebrafish neuromuscular junction PNAS 107 13906 13911 10.1073/pnas.1008598107 20643933 PMC2922265 · DOI
  69. Willems J de Jong APH Scheefhals N Mertens E Catsburg LAE Poorthuis RB de Winter F Verhaagen J Meye FJ MacGillavry HD 2020 ORANGE: A CRISPR/Cas9-based genome editing toolbox for epitope tagging of endogenous proteins in neurons PLOS Biology 18 e3000665 10.1371/journal.pbio.3000665 32275651 PMC7176289 · DOI
  70. Wolfes AC Dean C 2020 The diversity of synaptotagmin isoforms Current Opinion in Neurobiology 63 198 209 10.1016/j.conb.2020.04.006 32663762 · DOI
  71. Xie L Torigoe SE Xiao J Mai DH Li L Davis FP Dong P Marie-Nelly H Grimm J Lavis L Darzacq X Cattoglio C Liu Z Tjian R 2017 A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency Genes & Development 31 1795 1808 10.1101/gad.303321.117 28982762 PMC5666677 · DOI
  72. Yao J Gaffaney JD Kwon SE Chapman ER 2011a Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release Cell 147 666 677 10.1016/j.cell.2011.09.046 22036572 PMC3220409 · DOI · Paper page
  73. Yao J Kwon SE Gaffaney JD Dunning FM Chapman ER 2011b Uncoupling the roles of synaptotagmin I during endo- and exocytosis of synaptic vesicles Nature Neuroscience 15 243 249 10.1038/nn.3013 22197832 PMC3435110 · DOI
  74. Yoshihara M Littleton JT 2002 Synaptotagmin I functions as a calcium sensor to synchronize neurotransmitter release Neuron 36 897 908 10.1016/S0896-6273(02)01065-6 12467593 · DOI · Paper page
  75. Zhang C Wu B Beglopoulos V Wines-Samuelson M Zhang D Dragatsis I Südhof TC Shen J 2009 Presenilins are essential for regulating neurotransmitter release Nature 460 632 636 10.1038/nature08177 19641596 PMC2744588 · DOI
  76. Zhao H Ito Y Chappel J Andrews NW Teitelbaum SL Ross FP 2008 Synaptotagmin VII regulates bone remodeling by modulating osteoclast and osteoblast secretion Developmental Cell 14 914 925 10.1016/j.devcel.2008.03.022 18539119 PMC2480494 · DOI

Cited by

Sorted by citations

Authors
Vevea, J. D., Kusick, G. F., Courtney, K. C., Chen, E., Watanabe, S., & Chapman, E. R.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Johns Hopkins University (US)
Corresponding author
Chapman, Edwin R
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2021-09-20
Volume
10
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.67261
PMC
PMC8452306
OpenAlex
W3201247469
Cited by
51
References
7
Citations by year
2026: 11 · 2025: 10 · 2024: 12 · 2023: 7 · 2022: 10
FWCI
3.79
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 Institutes of Health (MH061876, NS097362, NS098604, NS111133-01, NS105810-01A1, GM007445, S10RR026445)
  • National Science Foundation (1727260, 2016217537)
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
synaptotagmin 7, synaptic vesicle docking, palmitoylation, presynaptic function, glutamate release, synaptic vesicle replenishment, paired-pulse facilitation, asynchronous release, peripheral membrane proteins, hippocampal neurons, synaptic plasticity
MeSH terms
Animals, Axons, Cell Membrane, Cells, Cultured, Exocytosis, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Protein Processing, Post-Translational, Synaptic Vesicles, Time Factors, Rats, Sprague-Dawley, Mice, Knockout, Protein Transport, Synaptotagmins, Mice, Rats, Amyloid Precursor Protein Secretases, Lipoylation, Proteolysis, Molecular Docking Simulation

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