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Pathogenic mutations in clathrin heavy chain disrupt synapse architecture and learning in <i>Drosophila</i>.

Overview

Authors: Jyoti Das1,2, Manisha Datta1,3, Srikanth Pippadpally4, Bhavika Jethani1, Surya Bansi Singh1, Avinash Kshirsagar1, Akankhya Jena1, Vimlesh Kumar4, Amitabha Majumdar1, Deepa Subramanyam1
ORCID iDs: Jyoti Das, Deepa Subramanyam
  1. National Centre for Cell Science, S.P. Pune University, Ganeshkhind Road, Pune, Maharashtra 411007, India
  2. Savitribai Phule Pune University, Pune, Maharashtra 411007, India
  3. Regional Centre for Biotechnology, Faridabad, Haryana 121001, India
  4. Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, Madhya Pradesh 462 066, India
Institutions: National Centre for Cell Science (India); Savitribai Phule Pune University (India); Regional Centre for Biotechnology (India); Indian Institute of Science Education and Research, Bhopal (India)
Journal: iScience, volume 29, issue 7, article 116317
Dates: received 22 September 2025; accepted 25 May 2026; published online 11 June 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.isci.2026.116317 · PMID 42325560 · PMCID PMC13276152 · OpenAlex W7164364508
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), drosophila (organism), cellular / molecular (subfield)
Methods: Evoked potentials, fMRI & imaging, Statistics
Keywords: molecular biology, developmental biology
Topic: Cellular transport and secretion (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Science and Engineering Research Board (CRG/2021/00599); India Ministry of Science & Technology Department of Biotechnology (BT/PR43190/MED/97/573/2021); Department of Science and Technology, Ministry of Science and Technology, India; University Grants Commission
Citations: not cited yet (Europe PMC); 39 references in the paper
Research resources: nc82 RRID:AB_2314866, RRID:AB_2338964, RRID:AB_2338967, Alexa Flour 647 goat anti-mouse RRID:AB_2535804, Discs Large (Dlg) RRID:AB_528203, FasII RRID:AB_528235, GluRIIA RRID:AB_528269, Spectrin RRID:AB_528473

Abstract

Clathrin-mediated endocytosis is essential for neural development and function. Recent studies have linked de novo mutations in the clathrin heavy-chain gene to a range of neurodevelopmental disorders. In this study, we have modeled two pathogenic mutations, L1047P and W1108R, in Drosophila melanogaster and examined their effects on vesicle dynamics, ligand uptake, neuronal development, and memory formation. Our data show that expression of these mutant forms of clathrin heavy chain results in reduced survival and defective learning when expressed ubiquitously or exclusively in neurons. These mutations also disrupted vesicle dynamics and reduced ligand uptake under conditions of heat stress. While no obvious defects in neuronal morphology and function were observed at the larval neuromuscular junction, we noticed significant disruptions in the expression of markers associated with synapse maturation. Overall, our study establishes a model that can provide insights into the cellular basis of clathrin heavy-chain-related neurodevelopmental disorders.

Reproduced under the paper's license (CC BY-NC), 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

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Data

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Data and code availability

Data reported in this paper will be shared by the lead contact upon request.

This study does not report any original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead author upon request.

Reproduced under the paper's license (CC BY-NC), 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 2, 28 September 2026

  • Authors: added Deepa Subramanyam (0000-0002-1650-5690); removed Deepa Subramanyam

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 2 keywords, 4 funders, 39 references, 8 RRIDs.

Cite

This paper

Das, J., Datta, M., Pippadpally, S., Jethani, B., Singh, S. B., Kshirsagar, A., Jena, A., Kumar, V., Majumdar, A., & Subramanyam, D. (2026). Pathogenic mutations in clathrin heavy chain disrupt synapse architecture and learning in <i>Drosophila</i>. iScience, 29(7), 116317. https://doi.org/10.1016/j.isci.2026.116317

BibTeX

@article{das2026pathogenic,
author = {Das, Jyoti and Datta, Manisha and Pippadpally, Srikanth and Jethani, Bhavika and Singh, Surya Bansi and Kshirsagar, Avinash and Jena, Akankhya and Kumar, Vimlesh and Majumdar, Amitabha and Subramanyam, Deepa},
title = {{Pathogenic mutations in clathrin heavy chain disrupt synapse architecture and learning in \<i\>Drosophila\</i\>}},
journal = {iScience},
year = {2026},
month = jun,
volume = {29},
number = {7},
pages = {116317},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.116317},
url = {https://doi.org/10.1016/j.isci.2026.116317},
pmid = {42325560},
pmcid = {PMC13276152}
}

RIS

TY - JOUR
AU - Das, Jyoti
AU - Datta, Manisha
AU - Pippadpally, Srikanth
AU - Jethani, Bhavika
AU - Singh, Surya Bansi
AU - Kshirsagar, Avinash
AU - Jena, Akankhya
AU - Kumar, Vimlesh
AU - Majumdar, Amitabha
AU - Subramanyam, Deepa
TI - Pathogenic mutations in clathrin heavy chain disrupt synapse architecture and learning in <i>Drosophila</i>
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/06/11
VL - 29
IS - 7
SP - 116317
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.116317
UR - https://doi.org/10.1016/j.isci.2026.116317
LA - en
ER -

CSL-JSON

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