A conserved Arf-GEF modulates axonal integrity through RAB-35 by altering neuron-epidermal attachment.
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Overview
- Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia
- School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, 4072, Australia
Abstract
Neurites of sensory neurons innervate the skin and are embedded within it. These delicate structures are chronically exposed to mechanical strain and yet their integrity is maintained throughout life. In C. elegans, UNC-70 (a β-spectrin protein) functions in synergy with the small GTPase RAB-35 within the skin to stabilize neuron–epidermal attachment against mechanical strain and prevent movement-induced damage to mechanosensitive axons. However, the molecular pathway regulating these specialized attachments remains elusive. Here, through an unbiased genetic screen, we have identified a guanine nucleotide exchange factor (GEF), AGEF-1, that impacts axonal maintenance. This molecule is known to function in endocytic recycling and its human ortholog, BIG2 (also known as ARFGEF2), is associated with the development of the periventricular nodular heterotopia. We show that AGEF-1 functions selectively within the skin to regulate axonal integrity of mechanosensitive neurons. Mechanistically, we reveal that AGEF-1 binds to epidermal RAB-35 and regulates its activity, modulating neuron–epidermal attachment stability. Finally, we demonstrate that this GEF is highly conserved, with its human ortholog BIG2 being capable of replacing AGEF-1. Together, we reveal the molecular machinery responsible for fine-tuning neuron–epidermal attachments and maintaining axonal integrity during life.
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Zenodo 6031709
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
- 27 September 2026: the link answers (HTTP 200)
8 files
- __init__.py — Python, 1 line
- __main__.py — Python, 8 lines
- alert_dialog.py — Python, 19 lines
- constants.py — Python, 15 lines
- group_summarizer.py — Python, 230 lines
- gui_main_dialog.py — Python, 235 lines
- LICENSE — License, 674 lines
- README.md — Text, 62 lines
igorbonap/signal-probability-along-line
65e8a5fa00026476a5077d63fee69c191b3ebd9f, 10 February 2022Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
8 files
- __init__.py — Python, 1 line
- __main__.py — Python, 8 lines
- alert_dialog.py — Python, 19 lines
- constants.py — Python, 15 lines
- group_summarizer.py — Python, 230 lines
- gui_main_dialog.py — Python, 235 lines
- LICENSE — License, 674 lines
- README.md — Text, 65 lines
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Version 2, 28 September 2026
- Publisher: — → The Company of Biologists
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 6 keywords, 10 MeSH terms, 4 funders, 55 references.
Cite
This paper
Bonacossa-Pereira, I., Le, D., Coakley, S., & Hilliard, M. A. (2026). A conserved Arf-GEF modulates axonal integrity through RAB-35 by altering neuron-epidermal attachment. Journal of cell science, 139(13), jcs264565. https://
BibTeX
@article{bonacossapereir
author = {Bonacossa-Pereira, Igor and Le, Dat and Coakley, Sean and Hilliard, Massimo A.},
title = {{A conserved Arf-GEF modulates axonal integrity through RAB-35 by altering neuron-epidermal attachment}},
journal = {Journal of cell science},
year = {2026},
month = jul,
volume = {139},
number = {13},
pages = {jcs264565},
publisher = {The Company of Biologists},
issn = {0021-9533},
doi = {10.1242/
url = {https://
pmid = {42312793},
pmcid = {PMC13405217}
}
RIS
TY - JOUR
AU - Bonacossa-Pereira, Igor
AU - Le, Dat
AU - Coakley, Sean
AU - Hilliard, Massimo A.
TI - A conserved Arf-GEF modulates axonal integrity through RAB-35 by altering neuron-epidermal attachment
T2 - Journal of cell science
J2 - J Cell Sci
PY - 2026
DA - 2026/
VL - 139
IS - 13
SP - jcs264565
SN - 0021-9533
PB - The Company of Biologists
DO - 10.1242/
UR - https://
LA - en
ER -
CSL-JSON
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