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A versatile nanobody platform for live and super-resolution imaging of synaptic vesicle dynamics and plasticity in rodent and human neurons.

Overview

Authors: Rashi Goel1, Kristina Jevdokimenko2, Ronja Rehm2, Jannik Hentze2,3, Paola Agüi-Gonzalez2, Momchil Ninov4, Erik Maier2, Yin Wu2, Felix Lange5,6, Agata Witkowska7,8, Svenja Bolz7, Francesca Pennacchietti9, Martina Damenti9, Natalie Kaempf10,11, Vladimir Khayenko12, Carles Calatayud10,11, Viveka Nand Malviya1, Natali L. Chanaday13, Emma Scaletti Hutchinson14, Hao Liu14
and 22 other authorsKirsten Weyand15, Valentin Schwarze15, Daniela Ivanova16,17,18, Tristan P. Wallis19, Christopher Small19, Hans M. Maric12, Merja Joensuu19,20, Michael A. Cousin16,17,18, Frédéric A. Meunier19,21, Patrik Verstreken10,11, Ilaria Testa9, Ege T. Kavalali22,23, Volker Haucke7,8,24, Stefan Jakobs5,6,25, Henning Urlaub4,26,27, Nils Brose15, Benjamin H. Cooper15, Pål Stenmark14, Felipe Opazo2,3,28, Reinhard Jahn1, Silvio O. Rizzoli2,3, Eugenio F. Fornasiero2,29
29 affiliations
  1. Laboratory of Neurobiology, Max Planck Institute for Multidisciplinary Sciences,37077 Göttingen, Germany
  2. Institute of Neuro- and Sensory Physiology, University Medical Center Göttingen,37073 Göttingen, Germany
  3. Center for Biostructural Imaging of Neurodegeneration (BIN), University Medical Center Göttingen,37075 Göttingen, Germany
  4. Bioanalytical Mass Spectrometry Research Group, Max Planck Institute for Multidisciplinary Sciences,37077 Göttingen, Germany
  5. Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences,37077 Göttingen, Germany
  6. Clinic of Neurology, University Medical Center Göttingen,37075 Göttingen, Germany
  7. Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP),13125 Berlin, Germany
  8. NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin,10117 Berlin, Germany
  9. Department of Applied Physics and SciLifeLab, KTH Royal Institute of Technology,Stockholm, 17165 Sweden
  10. 8 VIB-KU Leuven Center for Neuroscience, Leuven, 3000 Belgium
  11. Department of Neurosciences, Leuven Brain Institute, Belgium and KU Leuven,Leuven, 3000 Belgium
  12. Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Wuerzburg,97080 Wuerzburg, Germany
  13. Department of Physiology, Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA 19104 USA
  14. Department of Biochemistry and Biophysics, Stockholm University,Stockholm, SE-106 91 Sweden
  15. Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences,37075 Göttingen, Germany
  16. Centre for Discovery Brain Sciences, University of Edinburgh,Hugh Robson Building, George Square, Edinburgh, Scotland UK
  17. Simons Initiative for the Developing Brain, University of Edinburgh,Hugh Robson Building, Edinburgh, EH8 9XD Scotland UK
  18. Muir Maxwell Epilepsy Centre, University of Edinburgh,Hugh Robson Building, Edinburgh, EH8 9XD Scotland UK
  19. Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland,Brisbane, QLD 4072 Australia
  20. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland,Brisbane, QLD 4072 Australia
  21. School of Biomedical Sciences, The University of Queensland,Brisbane, QLD 4072 Australia
  22. Department of Pharmacology, School of Medicine, Vanderbilt University,Nashville, TN 37240-7933 USA
  23. Vanderbilt Brain Institute, Vanderbilt University,Nashville, TN 37240-7933 USA
  24. Faculty of Biology, Freie Universität Berlin,14195 Chemistry, Pharmacy, Berlin, Germany
  25. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Translational Neuroinflammation and Automated Microscopy,37075 Göttingen, Germany
  26. Bioanalytics, Department of Clinical Chemistry, University Medical Center Göttingen,37075 Göttingen, Germany
  27. Cluster of Excellence ″Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells″ (MBExC), University of Göttingen,37075 Göttingen, Germany
  28. NanoTag Biotechnologies GmbH, 37079 Göttingen, Germany
  29. Department of Life Sciences, University of Trieste,Trieste, 34127 Italy
Journal: Journal of nanobiotechnology, volume 24, issue 1, article 443
Dates: received 21 July 2025; accepted 15 April 2026; published online 14 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s12951-026-04489-w · PMID 42135832 · PMCID PMC13185310 · OpenAlex W7161125234
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), rat (organism), cellular / molecular (subfield)
Methods: Statistics, Machine learning, Evoked potentials, fMRI & imaging
Keywords: Nanotools, Synaptic vesicles, Synaptotagmin, Presynaptic biology, Nanobodies, SdAb, Biomedical engineering
MeSH: Neuronal Plasticity*, Neurons*, Single-Domain Antibodies*, Synaptic Vesicles*, Animals, Endocytosis, Humans, Mice, Rats, Synaptic Transmission, Synaptotagmin I (* major topic)
Topic: Cellular transport and secretion (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Herzzentrum Göttingen (1018)
Citations: cited by 1 paper (Europe PMC); 91 references in the paper

Abstract

Synaptic neurotransmission is a critical hallmark of brain activity and one of the first processes affected in neural diseases. Monitoring this process, particularly synaptic vesicle recycling, in living cells has been instrumental in revealing the mechanisms responsible for neurotransmitter release. However, currently available reporters suffer from limitations, such as large probe sizes or limited compatibility for human neurons, hampering the quantitative analysis of synaptic pathophysiology. Here, we describe the NbLumSyt1 toolkit, a panel of nanobody-based affinity probes that target the luminal domain of the synaptic vesicle protein Synaptotagmin 1 (Syt1). These new tools enable quantitative, noninvasive imaging and functional interrogation of Syt1 exo-endocytosis and trafficking in human neurons, with unprecedented precision, versatility and cost efficiency, in technologies ranging from fixed- and live-cell super-resolution imaging to electron microscopy and mass spectrometry. Overall, NbLumSyt1 nanobinders provide a valuable platform for studying synaptic physiology and pathophysiology, benefiting fundamental neuroscience and translational efforts to study and develop treatments for brain-related disorders.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12951-026-04489-w.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

Data is provided within the manuscript or supplementary information files.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 42 authors, 7 keywords, 11 MeSH terms, 1 funder, 86 references, 16 RRIDs.

Cite

This paper

Goel, R., Jevdokimenko, K., Rehm, R., Hentze, J., Agüi-Gonzalez, P., Ninov, M., Maier, E., Wu, Y., Lange, F., Witkowska, A., Bolz, S., Pennacchietti, F., Damenti, M., Kaempf, N., Khayenko, V., Calatayud, C., Malviya, V. N., Chanaday, N. L., Hutchinson, E. S., . . . Fornasiero, E. F. (2026). A versatile nanobody platform for live and super-resolution imaging of synaptic vesicle dynamics and plasticity in rodent and human neurons. Journal of nanobiotechnology, 24(1), 443. https://doi.org/10.1186/s12951-026-04489-w

BibTeX

@article{goel2026versatile,
author = {Goel, Rashi and Jevdokimenko, Kristina and Rehm, Ronja and Hentze, Jannik and Agüi-Gonzalez, Paola and Ninov, Momchil and Maier, Erik and Wu, Yin and Lange, Felix and Witkowska, Agata and Bolz, Svenja and Pennacchietti, Francesca and Damenti, Martina and Kaempf, Natalie and Khayenko, Vladimir and Calatayud, Carles and Malviya, Viveka Nand and Chanaday, Natali L. and Hutchinson, Emma Scaletti and Liu, Hao and Weyand, Kirsten and Schwarze, Valentin and Ivanova, Daniela and Wallis, Tristan P. and Small, Christopher and Maric, Hans M. and Joensuu, Merja and Cousin, Michael A. and Meunier, Frédéric A. and Verstreken, Patrik and Testa, Ilaria and Kavalali, Ege T. and Haucke, Volker and Jakobs, Stefan and Urlaub, Henning and Brose, Nils and Cooper, Benjamin H. and Stenmark, Pål and Opazo, Felipe and Jahn, Reinhard and Rizzoli, Silvio O. and Fornasiero, Eugenio F.},
title = {{A versatile nanobody platform for live and super-resolution imaging of synaptic vesicle dynamics and plasticity in rodent and human neurons}},
journal = {Journal of nanobiotechnology},
year = {2026},
month = may,
volume = {24},
number = {1},
pages = {443},
publisher = {BMC},
issn = {1477-3155},
doi = {10.1186/s12951-026-04489-w},
url = {https://doi.org/10.1186/s12951-026-04489-w},
pmid = {42135832},
pmcid = {PMC13185310}
}

RIS

TY - JOUR
AU - Goel, Rashi
AU - Jevdokimenko, Kristina
AU - Rehm, Ronja
AU - Hentze, Jannik
AU - Agüi-Gonzalez, Paola
AU - Ninov, Momchil
AU - Maier, Erik
AU - Wu, Yin
AU - Lange, Felix
AU - Witkowska, Agata
AU - Bolz, Svenja
AU - Pennacchietti, Francesca
AU - Damenti, Martina
AU - Kaempf, Natalie
AU - Khayenko, Vladimir
AU - Calatayud, Carles
AU - Malviya, Viveka Nand
AU - Chanaday, Natali L.
AU - Hutchinson, Emma Scaletti
AU - Liu, Hao
AU - Weyand, Kirsten
AU - Schwarze, Valentin
AU - Ivanova, Daniela
AU - Wallis, Tristan P.
AU - Small, Christopher
AU - Maric, Hans M.
AU - Joensuu, Merja
AU - Cousin, Michael A.
AU - Meunier, Frédéric A.
AU - Verstreken, Patrik
AU - Testa, Ilaria
AU - Kavalali, Ege T.
AU - Haucke, Volker
AU - Jakobs, Stefan
AU - Urlaub, Henning
AU - Brose, Nils
AU - Cooper, Benjamin H.
AU - Stenmark, Pål
AU - Opazo, Felipe
AU - Jahn, Reinhard
AU - Rizzoli, Silvio O.
AU - Fornasiero, Eugenio F.
TI - A versatile nanobody platform for live and super-resolution imaging of synaptic vesicle dynamics and plasticity in rodent and human neurons
T2 - Journal of nanobiotechnology
J2 - J Nanobiotechnology
PY - 2026
DA - 2026/05/14
VL - 24
IS - 1
SP - 443
SN - 1477-3155
PB - BMC
DO - 10.1186/s12951-026-04489-w
UR - https://doi.org/10.1186/s12951-026-04489-w
LA - en
ER -

CSL-JSON

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"issued": {
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}

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