OSCR

NSF is required for diverse endocytic modes by promoting fusion and fission pore closure in secretory cells.

Overview

Authors: Xin-Sheng Wu1, Tao Sun1, Bo Shi1, Sunghoon Lee1, Zheng Zhang1, Lisi Wei1, Xin Wang1, Maryam Molakarimi1, Sue Han1, Aaron Uy1, Lin Gan2, Ling-Gang Wu1
ORCID iDs: Ling-Gang Wu
  1. National Institute of Neurological Disorders and Stroke, 35 Convent Dr, Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA
  2. Flaum Eye Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA
Institutions: National Institute of Neurological Disorders and Stroke (United States); University of Rochester Medicine (United States); University of Rochester (United States)
Journal: iScience, volume 29, issue 5, article 115510
Dates: received 18 August 2025; accepted 24 March 2026; published online 27 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.115510 · PMID 42004027 · PMCID PMC13091539 · OpenAlex W7141154165
Open access: gold, a free copy (OpenAlex)
Status: code on request (how the code is found and verified)
Categories: cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Preprocessing, Evoked potentials, fMRI & imaging
Keywords: Neuroscience, Cellular neuroscience
Topic: Cellular transport and secretion (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Institutes of Health; National Institute of Neurological Disorders and Stroke; U.S. Department of Health and Human Services
Citations: not cited yet (Europe PMC); 50 references in the paper
Research resources: RRID:AB_2083165, Mouse Monoclonal anti-dynamin 1 RRID:AB_2093212, Rabbit polyclonal anti-AP2 RRID:AB_2115072, Mouse monoclonal anti-NSF-1 RRID:AB_2155806, Mouse monoclonal anti-β-actin RRID:AB_2223210, Rabbit Monoclonal anti-dynamin 2 RRID:AB_3739825, Rabbit monoclonal anti-TAU RRID:AB_778254, Mouse: C57BL/6J RRID:IMSR_JAX, EPC-10 Amplifier RRID:SCR_018399

Abstract

The ATPase N-ethylmaleimide-sensitive factor (NSF), known for disassembling SNARE complexes, plays key roles in neurotransmitter release, neurotransmitter (AMPA, GABA, and dopamine) receptor trafficking, and synaptic plasticity, and its dysfunction or mutation is linked to neurological disorders. These roles are largely attributed to SNARE-mediated exocytosis. Here, we reveal an unexpected role for NSF: mediating diverse modes of endocytosis—including slow, fast, ultrafast, overshoot, and bulk—by driving closure of both fusion and fission pores. This function was consistently observed across large calyx nerve terminals, small hippocampal boutons, and chromaffin cells using capacitance recordings, synapto-pHluorin imaging, electron microscopy, and multi-color pore-closure imaging. Results were robust across four NSF inhibitors, gene knockout, knockdown, and mutations. Furthermore, NSF facilitates content release. These findings establish NSF as a central regulator of membrane fission, kiss-and-run fusion, endocytosis, and exo-endocytosis coupling, providing a mechanistic basis for its diverse roles in synaptic transmission, receptor trafficking, and disease.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

No dataset and no data link were found in the paper.

Data and code availability

All data produced for this manuscript are available from the lead contact () upon reasonable request. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the corresponding author upon request.

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, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 2 keywords, 3 funders, 50 references, 9 RRIDs.

Cite

This paper

Wu, X.-S., Sun, T., Shi, B., Lee, S., Zhang, Z., Wei, L., Wang, X., Molakarimi, M., Han, S., Uy, A., Gan, L., & Wu, L.-G. (2026). NSF is required for diverse endocytic modes by promoting fusion and fission pore closure in secretory cells. iScience, 29(5), 115510. https://doi.org/10.1016/j.isci.2026.115510

BibTeX

@article{wu2026nsf,
author = {Wu, Xin-Sheng and Sun, Tao and Shi, Bo and Lee, Sunghoon and Zhang, Zheng and Wei, Lisi and Wang, Xin and Molakarimi, Maryam and Han, Sue and Uy, Aaron and Gan, Lin and Wu, Ling-Gang},
title = {{NSF is required for diverse endocytic modes by promoting fusion and fission pore closure in secretory cells}},
journal = {iScience},
year = {2026},
month = mar,
volume = {29},
number = {5},
pages = {115510},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.115510},
url = {https://doi.org/10.1016/j.isci.2026.115510},
pmid = {42004027},
pmcid = {PMC13091539}
}

RIS

TY - JOUR
AU - Wu, Xin-Sheng
AU - Sun, Tao
AU - Shi, Bo
AU - Lee, Sunghoon
AU - Zhang, Zheng
AU - Wei, Lisi
AU - Wang, Xin
AU - Molakarimi, Maryam
AU - Han, Sue
AU - Uy, Aaron
AU - Gan, Lin
AU - Wu, Ling-Gang
TI - NSF is required for diverse endocytic modes by promoting fusion and fission pore closure in secretory cells
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/03/27
VL - 29
IS - 5
SP - 115510
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.115510
UR - https://doi.org/10.1016/j.isci.2026.115510
LA - en
ER -

CSL-JSON

{
"id": "10.1016/j.isci.2026.115510",
"type": "article-journal",
"title": "NSF is required for diverse endocytic modes by promoting fusion and fission pore closure in secretory cells",
"container-title": "iScience",
"author": [
{
"family": "Wu",
"given": "Xin-Sheng"
},
{
"family": "Sun",
"given": "Tao"
},
{
"family": "Shi",
"given": "Bo"
},
{
"family": "Lee",
"given": "Sunghoon"
},
{
"family": "Zhang",
"given": "Zheng"
},
{
"family": "Wei",
"given": "Lisi"
},
{
"family": "Wang",
"given": "Xin"
},
{
"family": "Molakarimi",
"given": "Maryam"
},
{
"family": "Han",
"given": "Sue"
},
{
"family": "Uy",
"given": "Aaron"
},
{
"family": "Gan",
"given": "Lin"
},
{
"family": "Wu",
"given": "Ling-Gang"
}
],
"container-title-short": "iScience",
"volume": "29",
"issue": "5",
"page": "115510",
"DOI": "10.1016/j.isci.2026.115510",
"PMID": "42004027",
"PMCID": "PMC13091539",
"ISSN": "2589-0042",
"publisher": "Elsevier",
"URL": "https://doi.org/10.1016/j.isci.2026.115510",
"language": "en",
"issued": {
"date-parts": [
[
2026,
3,
27
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1016/j.isci.2025.112000
Actin maintains synaptic transmission by restraining vesicle release probability.
Journal: iScience
In common: cellular / molecular, 15 references, author Ling-Gang Wu
[2] doi:10.1111/jnc.70551 [code]
Synaptobrevin-2 Containing Extracellular Vesicles Are Rapidly Incorporated Into Mammalian Neurons via a Dynamin-Dependent Pathway.
Journal: Journal of neurochemistry
In common: cellular / molecular, 4 references
[3] doi:10.1038/s41467-023-42497-8
Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration.
Journal: Nature communications
In common: cellular / molecular, 3 references
[4] doi:10.1038/s41467-023-38595-2 [code]
Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis.
Journal: Nature communications
In common: cellular / molecular, 3 references
[5] doi:10.1016/j.isci.2024.111156
SNARE protein SNAP25 regulates the chloride-transporter KCC2 in neurons.
Journal: iScience
In common: cellular / molecular, 2 references
[6] doi:10.1126/sciadv.adq6477 [code]
Dynamic regulation of vesicle pools in a detailed spatial model of the complete synaptic vesicle cycle.
Journal: Science advances
In common: cellular / molecular, 2 references
[7] doi:10.1016/j.celrep.2024.114026 [code]
Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles.
Journal: Cell reports
In common: cellular / molecular, 2 references
[8] doi:10.1186/s13578-025-01458-y [code]
Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.
Journal: Cell & bioscience
In common: cellular / molecular, 2 references
[9] doi:10.1371/journal.pcbi.1011720 [code]
How Merkel cells transduce mechanical stimuli: A biophysical model of Merkel cells.
Journal: PLoS computational biology
In common: 2 references
[10] doi:10.7554/elife.107276 [code]
Deployment of endocytic machinery to periactive zones of nerve terminals is independent of active zone assembly and evoked release.
Journal: eLife
In common: cellular / molecular, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: code errors and mismatches between the code and the paper about this paper and its code, from readers and its authors, beside the paper and its tracing map.

Reproductions: reports from readers who ran the authors' code and did not get the paper's result, what they ran, with which environment, commit and data.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.