CoChat
Sign Up
Cited by 40Cellular transport and secretionNeuroscience and Neuropharmacology ResearchExtracellular vesicles in disease

Rebuilding essential active zone functions within a synapse

Open access
Tan, Chao, Wang, Shan Shan H., de Nola, Giovanni, Kaeser, Pascal S.·2022·Neuron
DOI 10.1016/j.neuron.2022.01.026PMC PMC9081183
Open this paper in CoChat — free account

Abstract

Presynaptic active zones are molecular machines that control neurotransmitter secretion. They form sites for vesicle docking and priming and couple vesicles to Ca 2+ entry for release triggering. The complexity of active zone machinery has made it challenging to determine its mechanisms in release. Simultaneous knockout of the active zone proteins RIM and ELKS disrupts active zone assembly, abolishes vesicle docking, and impairs release. We here rebuild docking, priming, and Ca 2+ secretion coupling in these mutants without reinstating active zone networks. Re-expression of RIM zinc fingers recruited Munc13 to undocked vesicles and rendered the vesicles release competent. Action potential triggering of release was reconstituted by docking these primed vesicles to Ca 2+ channels through attaching RIM zinc fingers to Ca V β4-subunits. Our work identifies an 80-kDa β4-Zn protein that bypasses the need for megadalton-sized secretory machines, establishes that fusion competence and docking are mechanistically separable, and defines RIM zinc finger-Munc13 complexes as hubs for active zone function.

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 · 10.1016/j.neuron.2022.01.026

Cites

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?

Self-check

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

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

The citation lists haven’t been fetched yet

References 100 · Cited by 40

Research works printed but not linked: 83

  1. Acuna C, Liu X, Gonzalez A, and Südhof TC (2015). RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release. Neuron 87, 1234– 1247. 26402606
  2. Acuna C, Liu X, and Südhof TC (2016). How to Make an Active Zone: Unexpected Universal Functional Redundancy between RIMs and RIM-BPs. Neuron 91, 792– 807. 27537484
  3. Akil O, Dyka F, Calvet C, Emptoz A, Lahlou G, Nouaille S, Boutet de Monvel J, Hardelin J-P, Hauswirth WW, Avan P, (2019). Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model. Proc. Natl. Acad. Sci. U. S. A 116, 4496– 4501. 30782832 PMC6410774
  4. Al-Moyed H, Cepeda AP, Jung S, Moser T, Kügler S, and Reisinger E (2019). A dual-AAV approach restores fast exocytosis and partially rescues auditory function in deaf otoferlin knock-out mice. EMBO Mol. Med 11, 4496– 4501. PMC6328916 30509897
  5. Aravamudan B, Fergestad T, Davis WS, Rodesch CK, and Broadie K (1999). Drosophila UNC-13 is essential for synaptic transmission. Nat. Neurosci 2, 965– 971. 10526334
  6. Augustin I, Rosenmund C, Südhof TC, and Brose N (1999). Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 400, 457– 461. 10440375
  7. Basu J, Shen N, Dulubova I, Lu J, Guan R, Guryev O, Grishin NV, Rosenmund C, and Rizo J (2005). A minimal domain responsible for Munc13 activity. Nat Struct Mol Biol 12, 1017– 1018. 16228007
  8. Benarroch EE (2013). Synaptic vesicle exocytosis: Molecular mechanisms and clinical implications. Neurology 80, 1981– 1988. 23690298
  9. Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V, Rosenmund C, Rettig J, and Brose N (2001). Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron 30, 183– 196. 11343654
  10. Biederer T, Kaeser PS, and Blanpied TA (2017). Transcellular Nanoalignment of Synaptic Function. Neuron 96, 680– 696. 29096080 PMC5777221
  11. Breustedt J, Vogt KE, Miller RJ, Nicoll RA, and Schmitz D (2003). Alpha1E-containing Ca2+ channels are involved in synaptic plasticity. Proc. Natl. Acad. Sci. U. S. A 100, 12450– 12455. 14519849 PMC218778
  12. Brockmann MM, Maglione M, Willmes CG, Stumpf A, Bouazza BA, Velasquez LM, Grauel MK, Beed P, Lehmann M, Gimber N, (2019). RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses. Elife 8. PMC6752948 31535974
  13. Calakos N, Schoch S, Sudhof TC, Malenka RC, Südhof TC, Malenka RC, Sudhof TC, and Malenka RC (2004). Multiple roles for the active zone protein RIM1alpha in late stages of neurotransmitter release. Neuron 42, 889– 896. 15207234
  14. Camacho M, Basu J, Trimbuch T, Chang S, Pulido-Lozano C, Chang S-S, Duluvova I, Abo-Rady M, Rizo J, and Rosenmund C (2017). Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle docking and priming. Nat. Commun 8, 15293. 28489077 PMC5436228
  15. Cao YQ, Piedras-Renteria ES, Smith GB, Chen G, Harata NC, and Tsien RW (2004). Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. Neuron 43, 387– 400. 15294146
  16. Davydova D, Marini C, King C, Klueva J, Bischof F, Romorini S, Montenegro-Venegas C, Heine M, Schneider R, Schröder MS, (2014). Bassoon specifically controls presynaptic P/Q-type Ca(2+) channels via RIM-binding protein. Neuron 82, 181– 194. 24698275
  17. Dietrich D, Kirschstein T, Kukley M, Pereverzev A, von der Brelie C, Schneider T, and Beck H (2003). Functional Specialization of Presynaptic Cav2.3 Ca2+ Channels. Neuron 39, 483– 496. 12895422
  18. Dolphin AC (2012). Calcium channel auxiliary α2δ and β subunits: trafficking and one step beyond. Nat. Rev. Neurosci 13, 664– 664. 22805911
  19. Dong W, Radulovic T, Goral RO, Thomas C, Suarez Montesinos M, Guerrero-Given D, Hagiwara A, Putzke T, Hida Y, Abe M, (2018). CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse. Cell Rep. 24, 284– 293.e6. 29996090 PMC6372087
  20. Dulubova I, Lou X, Lu J, Huryeva I, Alam A, Schneggenburger R, Sudhof TC, and Rizo J (2005). A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity? EMBO J. 24, 2839– 2850. 16052212 PMC1187938
  21. Emperador-Melero J, Wong MY, Wang SSH, de Nola G, Nyitrai H, Kirchhausen T, and Kaeser PS (2021). PKC-phosphorylation of Liprin-α3 triggers phase separation and controls presynaptic active zone structure. Nat. Commun 12, 3057. 34031393 PMC8144191
  22. Fukuda M (2003). Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2. J. Biol. Chem 278, 15373– 80. 12578829
  23. Grauel MK, Maglione M, Reddy-Alla S, Willmes CG, Brockmann MM, Trimbuch T, Rosenmund T, Pangalos M, Vardar G, Stumpf A, (2016). RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. Proc. Natl. Acad. Sci 113, 11615– 11620. 27671655 PMC5068320
  24. Guzman GA, Guzman RE, Jordan N, and Hidalgo P (2019). A Tripartite Interaction Among the Calcium Channel α1- and β-Subunits and F-Actin Increases the Readily Releasable Pool of Vesicles and Its Recovery After Depletion. Front. Cell. Neurosci 13, 125. 31130843 PMC6509170
  25. Hammarlund M, Palfreyman MT, Watanabe S, Olsen S, and Jorgensen EM (2007). Open syntaxin docks synaptic vesicles. PLoS Biol. 5, e198. 17645391 PMC1914072
  26. Han W, Rhee J-S, Maximov A, Lao Y, Mashimo T, Rosenmund C, and Südhof TC (2004). N-glycosylation is essential for vesicular targeting of synaptotagmin 1. Neuron 41, 85– 99. 14715137
  27. Han Y, Kaeser PS, Südhof TC, and Schneggenburger R (2011). RIM determines Ca2+ channel density and vesicle docking at the presynaptic active zone. Neuron 69, 304– 316. 21262468 PMC3259453
  28. He E, Wierda K, van Westen R, Broeke JH, Toonen RF, Cornelisse LN, and Verhage M (2017). Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles. Nat. Commun 8, 15915. 28635948 PMC5482055
  29. Held RG, and Kaeser PS (2018). ELKS active zone proteins as multitasking scaffolds for secretion. Open Biol. 8, 170258. 29491150 PMC5830537
  30. Held RG, Liu C, and Kaeser PS (2016). ELKS controls the pool of readily releasable vesicles at excitatory synapses through its N-terminal coiled-coil domains. Elife 5. PMC4935463 27253063
  31. Held RG, Liu C, Ma K, Ramsey AM, Tarr TB, De Nola G, Wang SSH, Wang J, van den Maagdenberg AMJM, Schneider T, (2020). Synapse and Active Zone Assembly in the Absence of Presynaptic Ca2+ Channels and Ca2+ Entry. Neuron 107, 667– 683.e9. 32616470 PMC7442750
  32. Hibino H, Pironkova R, Onwumere O, Vologodskaia M, Hudspeth AJ, and Lesage F (2002). RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca(2+) channels. Neuron 34, 411– 423. 11988172 PMC2151925
  33. Hu C, Ahmed M, Melia TJ, Söllner TH, Mayer T, Rothman JE, Sollner TH, Mayer T, and Rothman JE (2003). Fusion of cells by flipped SNAREs. Science 300, 1745– 1749. 12805548
  34. Hudry E, and Vandenberghe LH (2019). Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality. Neuron 101, 839– 862. 30844402 PMC11804970
  35. Johnson S, Halford S, Morris AG, Patel RJ, Wilkie SE, Hardcastle AJ, Moore AT, Zhang K, and Hunt DM (2003). Genomic organisation and alternative splicing of human RIM1, a gene implicated in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81, 304– 314. 12659814
  36. de Jong APH, Roggero CM, Ho M-R, Wong MY, Brautigam CA, Rizo J, and Kaeser PS (2018). RIM C2B Domains Target Presynaptic Active Zone Functions to PIP2-Containing Membranes. Neuron 98, 335– 349.e7. 29606581 PMC5910229
  37. Kaeser PS, and Regehr WG (2017). The readily releasable pool of synaptic vesicles. Curr. Opin. Neurobiol 43, 63– 70. 28103533 PMC5447466
  38. Kaeser PS, Kwon HB, Chiu CQ, Deng L, Castillo PE, and Sudhof TC (2008). RIM1alpha and RIM1beta are synthesized from distinct promoters of the RIM1 gene to mediate differential but overlapping synaptic functions. J. Neurosci 28, 13435– 13447. 19074017 PMC2701653
  39. Kaeser PS, Deng L, Chávez AE, Liu X, Castillo PE, and Südhof TC (2009). ELKS2alpha/CAST deletion selectively increases neurotransmitter release at inhibitory synapses. Neuron 64, 227– 239. 19874790 PMC2785857
  40. Kaeser PS, Deng L, Wang Y, Dulubova I, Liu X, Rizo J, and Südhof TC (2011). RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction. Cell 144, 282– 295. 21241895 PMC3063406
  41. Kanaji S, Iwahashi J, Kida Y, Sakaguchi M, and Mihara K (2000). Characterization of the signal that directs Tom20 to the mitochondrial outer membrane. J. Cell Biol 151, 277– 288. 11038175 PMC2192658
  42. Kawabe H, Mitkovski M, Kaeser PS, Hirrlinger J, Opazo F, Nestvogel D, Kalla S, Fejtova A, Verrier SESE, Bungers SRSR, (2017). ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones. J. Cell Biol 216, 1143– 1161. 28264913 PMC5379939
  43. Kittel RJ, Wichmann C, Rasse TM, Fouquet W, Schmidt M, Schmid A, Wagh DA, Pawlu C, Kellner RR, Willig KI, (2006). Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 312, 1051– 1054. 16614170
  44. Koushika SP, Richmond JE, Hadwiger G, Weimer RM, Jorgensen EM, and Nonet ML (2001). A post-docking role for active zone protein Rim. Nat. Neurosci 4, 997– 1005. 11559854 PMC2585766
  45. Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K, Raja A, Coe BP, Stessman HA, He Z-X, (2015). Excess of rare, inherited truncating mutations in autism. Nat. Genet 47, 582– 588. 25961944 PMC4449286
  46. Kushibiki Y, Suzuki T, Jin Y, and Taru H (2019). RIMB-1/RIM-Binding Protein and UNC-10/RIM Redundantly Regulate Presynaptic Localization of the Voltage-Gated Calcium Channel in Caenorhabditis elegans. J. Neurosci 39, 8617– 8631. 31530643 PMC6820209
  47. Lin Y, McDonough SI, and Lipscombe D (2004). Alternative Splicing in the Voltage-Sensing Region of N-Type CaV2.2 Channels Modulates Channel Kinetics. J. Neurophysiol 92, 2820– 2830. 15201306
  48. Liu C, Bickford LS, Held RG, Nyitrai H, Südhof TC, and Kaeser PS (2014). The active zone protein family ELKS supports Ca2+ influx at nerve terminals of inhibitory hippocampal neurons. J. Neurosci 34, 12289– 12303. 25209271 PMC4160768
  49. Liu C, Kershberg L, Wang J, Schneeberger S, and Kaeser PS (2018). Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites. Cell 172, 706– 718.e15. 29398114 PMC5807134
  50. Liu KSY, Siebert M, Mertel S, Knoche E, Wegener S, Wichmann C, Matkovic T, Muhammad K, Depner H, Mettke C, (2011). RIM-binding protein, a central part of the active zone, is essential for neurotransmitter release. Science 334, 1565– 1569. 22174254
  51. Ma C, Su L, Seven AB, Xu Y, and Rizo J (2013). Reconstitution of the Vital Functions of Munc18 and Munc13 in Neurotransmitter Release. Science 339, 421– 425. 23258414 PMC3733786
  52. Matkovic T, Siebert M, Knoche E, Depner H, Mertel S, Owald D, Schmidt M, Thomas U, Sickmann A, Kamin D, (2013). The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles. J. Cell Biol 202, 667– 683. 23960145 PMC3747298
  53. McDonald NA, Fetter RD, and Shen K (2020). Assembly of synaptic active zones requires phase separation of scaffold molecules. Nature 588, 454– 458. 33208945
  54. Myoga MH, and Regehr WG (2011). Calcium Microdomains Near R-Type Calcium Channels Control the Induction of Presynaptic Long-Term Potentiation at Parallel Fiber to Purkinje Cell Synapses. J. Neurosci 31, 5235– 5243. 21471358 PMC3089026
  55. Nyitrai H, Wang SSH, and Kaeser PS (2020). ELKS1 Captures Rab6-Marked Vesicular Cargo in Presynaptic Nerve Terminals. Cell Rep. 31, 107712. 32521280 PMC7360120
  56. Oh KH, Krout MD, Richmond JE, and Kim H (2021). UNC-2 CaV2 Channel Localization at Presynaptic Active Zones Depends on UNC-10/RIM and SYD-2/Liprin-α in Caenorhabditis elegans. J. Neurosci 41, 4782– 4794. 33975919 PMC8260173
  57. Page KM, Rothwell SW, and Dolphin AC (2016). The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination. J. Biol. Chem 291, 20402– 20416. 27489103 PMC5034038
  58. Parthier D, Kuner T, and Körber C (2018). The presynaptic scaffolding protein Piccolo organizes the readily releasable pool at the calyx of Held. J. Physiol 596, 1485– 1499. 29194628 PMC5899986
  59. Pereverzev A, Mikhna M, Vajna R, Gissel C, Henry M, Weiergräber M, Hescheler J, Smyth N, and Schneider T (2002). Disturbances in Glucose-Tolerance, Insulin-Release, and Stress-Induced Hyperglycemia upon Disruption of the Cav2.3 (α1E) Subunit of Voltage-Gated Ca2+ Channels. Mol. Endocrinol 16, 884– 895. 11923483
  60. Quade B, Camacho M, Zhao X, Orlando M, Trimbuch T, Xu J, Li W, Nicastro D, Rosenmund C, and Rizo J (2019). Membrane bridging by Munc13-1 is crucial for neurotransmitter release. Elife 8. PMC6407922 30816091
  61. Reddy-Alla S, Bohme MA, Reynolds E, Beis C, Grasskamp AT, Mampell MM, Maglione M, Jusyte M, Rey U, Babikir H, (2017). Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission. Neuron 95, 1350– 1364.e12. 28867551
  62. Richmond JE, Davis WS, and Jorgensen EM (1999). UNC-13 is required for synaptic vesicle fusion in C. elegans. Nat. Neurosci 2, 959– 964. 10526333 PMC2585767
  63. Rosenmund C, and Stevens CF (1996). Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron 16, 1197– 1207. 8663996
  64. Schikorski T, and Stevens CF (2001). Morphological correlates of functionally defined synaptic vesicle populations. Nat. Neurosci 4, 391– 395. 11276229
  65. Schneider R, Hosy E, Kohl J, Klueva J, Choquet D, Thomas U, Voigt A, and Heine M (2015). Mobility of Calcium Channels in the Presynaptic Membrane. Neuron 86, 672– 679. 25892305
  66. Schoch S, Deák F, Königstorfer a, Mozhayeva M, Sara Y, Südhof TC, Kavalali ET, Deak F, Konigstorfer A, Mozhayeva M, (2001). SNARE function analyzed in synaptobrevin/VAMP knockout mice. Science 294, 1117– 1122. 11691998
  67. Schoch S, Castillo PE, Jo T, Mukherjee K, Geppert M, Wang Y, Schmitz F, Malenka RC, and Südhof TC (2002). RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 415, 321– 326. 11797009
  68. Siksou L, Varoqueaux F, Pascual O, Triller A, Brose N, and Marty S (2009). A common molecular basis for membrane docking and functional priming of synaptic vesicles. Eur. J. Neurosci 30, 49– 56. 19558619
  69. Spangler SA, Schmitz SK, Kevenaar JT, de Graaff E, de Wit H, Demmers J, Toonen RF, and Hoogenraad CC (2013). Liprin-alpha2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission. J. Cell Biol 201, 915– 928. 23751498 PMC3678157
  70. Sudhof TC (2004). The synaptic vesicle cycle. Annu. Rev. Neurosci 27, 509– 547. 15217342
  71. Sun J, and Roy S (2021). Gene-based therapies for neurodegenerative diseases. Nat. Neurosci PMC8394447 33526943
  72. Thevenon J, Callier P, Andrieux J, Delobel B, David A, Sukno S, Minot D, Mosca Anne L, Marle N, Sanlaville D, (2013). 12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech. Eur. J. Hum. Genet 21, 82– 88. 22713806 PMC3522191
  73. Todorov B, van de Ven RCG, Kaja S, Broos LAM, Verbeek SJ, Plomp JJ, Ferrari MD, Frants RR, and van den Maagdenberg AMJM (2006). Conditional inactivation of the Cacna1a gene in transgenic mice. Genesis 44, 589– 594. 17146767
  74. Tucker WC, Weber T, and Chapman ER (2004). Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs. Science 304, 435– 438. 15044754
  75. Varoqueaux F, Sigler A, Rhee JS, Brose N, Enk C, Reim K, and Rosenmund C (2002). Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proc. Natl. Acad. Sci. U. S. A 99, 9037– 9042. 12070347 PMC124419
  76. Verhage M, and Sørensen JB (2020). SNAREopathies: Diversity in Mechanisms and Symptoms. Neuron. 32559416
  77. Wang Y, Okamoto M, Schmitz F, Hofmann K, and Sudhof TC (1997). Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion. Nature 388, 593– 598. 9252191
  78. Wong MY, Liu C, Wang SSH, Roquas ACF, Fowler SC, and Kaeser PS (2018). Liprin-α3 controls vesicle docking and exocytosis at the active zone of hippocampal synapses. Proc. Natl. Acad. Sci. U. S. A 115, 2234– 2239. 29439199 PMC5834710
  79. Wu LG, Westenbroek RE, Borst JG, Catterall WA, and Sakmann B (1999). Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J. Neurosci 19, 726– 736. 9880593 PMC6782194
  80. Wu X, Cai Q, Shen Z, Chen X, Zeng M, Du S, and Zhang M (2019). RIM and RIM-BP Form Presynaptic Active-Zone-like Condensates via Phase Separation. Mol. Cell 73, 971– 984.e5. 30661983
  81. Wu X, Ganzella M, Zhou J, Zhu S, Jahn R, and Zhang M (2021). Vesicle Tethering on the Surface of Phase-Separated Active Zone Condensates. Mol. Cell 81, 13– 24.e7. 33202250
  82. Zhen M, and Jin Y (1999). The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature 401, 371– 375. 10517634
  83. Zucker RS, and Regehr WG (2002). Short-term synaptic plasticity. Annu. Rev. Physiol 64, 355– 405. 11826273

Authors
Tan, C., Wang, S. S. H., de Nola, G., & Kaeser, P. S.
Affiliations
Harvard University (US)
Corresponding author
Kaeser, Pascal S.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2022-05
Volume
110
Issue
9
Pages
1498-1515.e8
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2022.01.026
PMC
PMC9081183
OpenAlex
W4213266487
Cited by
40
References
100
Citations by year
2026: 8 · 2025: 6 · 2024: 12 · 2023: 6 · 2022: 8
FWCI
4.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NINDS (R01NS083898)
  • Giovanni Armenise-Harvard Foundation
  • National Institutes of Health
  • National Science Foundation (DGE1144152)
  • NIMH (R01MH113349)
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
active zone, neurotransmitter release, RIM, elk, Munc13, vesicle docking, vesicle priming
MeSH terms
Action Potentials, Synaptic Transmission, Synapses, Synaptic Vesicles, Presynaptic Terminals

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