---
title: "Nuclear LC3 Interactome Reveals Clathrin Heavy Chain Drives LC3 Nuclear Translocation in Trabecula"
id: "biorxiv-21-nuclear-lc3-interactome-profiling-identifies-clathrin-heavy-chain-as-a-mediator"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-21-nuclear-lc3-interactome-profiling-identifies-clathrin-heavy-chain-as-a-mediator"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.22.753497v1?rss=1"
published_at: "2026-09-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Nuclear LC3 Interactome Reveals Clathrin Heavy Chain Drives LC3 Nuclear Translocation in Trabecula
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-21-nuclear-lc3-interactome-profiling-identifies-clathrin-heavy-chain-as-a-mediator
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.22.753497v1?rss=1)
- **Published At:** 2026-09-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study profiled the **nuclear LC3** interactome in primary human trabecular meshwork (TM) cells using mass spectrometry of nuclear GFP-LC3 immunoprecipitates. Findings identify a reproducible set of nuclear LC3 partners enriched for proteins bearing **LIR/xLIR** motifs and reported nuclear localization. - **Clathrin heavy chain (CLTC)** was discovered as a previously unrecognized nuclear LC3-binding protein that colocalizes with nuclear LC3 puncta in TM cells. - Functional experiments showed that CLTC depletion reduced basal **LC3-II** levels, consistent with a role in autophagosome biogenesis, and impaired nuclear LC3 accumulation induced by nuclear export blockade and by cyclic mechanical stretch. - The impairment in nuclear LC3 accumulation occurred without changes in total CLTC abundance, indicating an active role for CLTC in promoting LC3 nuclear translocation rather than acting solely as a passive scaffold. - TM cells derived from glaucoma patients showed selective impairment of mechanically induced nuclear LC3 trafficking but retained comparable CLTC levels, suggesting a defect in coupling nuclear LC3 transport to **mechanotransduction** rather than a defect in the core transport machinery. - The data support that nuclear LC3 trafficking is an actively regulated, CLTC-dependent process linked to cytoskeletal and vesicular machinery, with potential relevance to nuclear homeostasis and glaucoma pathogenesis. - The work was supported by the National Eye Institute, BrightFocus Foundation, and Research to Prevent Blindness. The preprint has not been peer reviewed and the authors declared no competing interests.
## Clinical Analysis & Structured Key Points
Nuclear LC3 Interactome Profiling Identifies Clathrin Heavy Chain as a Mediator of Nuclear LC3 Translocation in Trabecular Meshwork Cells | bioRxiv Skip to main content New Results Nuclear LC3 Interactome Profiling Identifies Clathrin Heavy Chain as a Mediator of Nuclear LC3 Translocation in Trabecular Meshwork Cells View ORCID Profile Myoung Sup Shim , Chien-Chich Chou , Mi Sun Sung , Aleks Grimsrud , Vaibhav Desikan , Nikolai B Skiba , View ORCID Profile Paloma B Liton doi: https://doi.org/10.64898/2026.09.22.753497 Myoung Sup Shim Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Myoung Sup Shim Chien-Chich Chou Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mi Sun Sung Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aleks Grimsrud Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Vaibhav Desikan Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nikolai B Skiba Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paloma B Liton Duke University Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Paloma B Liton For correspondence: paloma.liton{at}duke.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract Although MAP1LC3B/LC3B (LC3) is best known as a cytoplasmic marker of autophagosome biogenesis, a substantial pool of LC3 resides in the nucleus and shuttles dynamically between nuclear and cytoplasmic compartments, yet the composition and regulation of this nuclear interactome remain poorly defined. Using mass spectrometry-based proteomic profiling of nuclear GFP-LC3 immunoprecipitates from primary human trabecular meshwork (TM) cells, a mechanosensitive ocular cell type, we identified a reproducible nuclear LC3 interactome enriched for proteins containing LC3-interacting region (LIR) and expanded LIR (xLIR) motifs and reported nuclear localization. Among these, clathrin heavy chain (CLTC) emerged as a previously unrecognized nuclear LC3 partner that localizes to the nucleus and colocalizes with nuclear LC3 puncta. CLTC depletion reduced basal LC3-II levels, consistent with a role in autophagosome biogenesis, and markedly impaired nuclear LC3 accumulation induced by both nuclear export blockade with leptomycin B and cyclic mechanical stretch, without altering total CLTC abundance, indicating that CLTC actively promotes LC3 nuclear translocation rather than serving as a passive scaffold. Strikingly, mechanical stress-induced nuclear LC3 trafficking, but not its basal component, was selectively impaired in TM cells derived from glaucoma patients, despite comparable CLTC levels, pointing to a defect in coupling this trafficking pathway to mechanotransduction rather than in the core transport machinery itself. Together, these findings establish nuclear LC3 trafficking as an actively regulated, CLTC-dependent process linked to cytoskeletal and vesicular machinery, and implicate its dysregulation in mechanically stressed glaucomatous cells, providing a framework for understanding how autophagy intersects with nuclear homeostasis, mechanotransduction, and glaucoma pathogenesis. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Eye Institute, https://ror.org/03wkg3b53 , EY026885 , EY033600 , EY005722 BrightFocus Foundation, https://ror.org/03cvfxv40 Research to Prevent Blindness Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 23, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share Nuclear LC3 Interactome Profiling Identifies Clathrin Heavy Chain as a Mediator of Nuclear LC3 Translocation in Trabecular Meshwork Cells Myoung Sup Shim , Chien-Chich Chou , Mi Sun Sung , Aleks Grimsrud , Vaibhav Desikan , Nikolai B Skiba , Paloma B Liton bioRxiv 2026.09.22.753497; doi: https://doi.org/10.64898/2026.09.22.753497 Share This Article: Copy Citation Tools Nuclear LC3 Interactome Profiling Identifies Clathrin Heavy Chain as a Mediator of Nuclear LC3 Translocation in Trabecular Meshwork Cells Myoung Sup Shim , Chien-Chich Chou , Mi Sun Sung , Aleks Grimsrud , Vaibhav Desikan , Nikolai B Skiba , Paloma B Liton bioRxiv 2026.09.22.753497; doi: https://doi.org/10.64898/2026.09.22.753497 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8021) Biochemistry (18781) Bioengineering (14921) Bioinformatics (44492) Biophysics (22625) Cancer Biology (19761) Cell Biology (26945) Clinical Trials (138) Developmental Biology (13993) Ecology (21037) Epidemiology (2067) Evolutionary Biology (25473) Genetics (16185) Genomics (23535) Immunology (18725) Microbiology (42548) Molecular Biology (18095) Neuroscience (93601) Paleontology (701) Pathology (2987) Pharmacology and Toxicology (5104) Physiology (8127) Plant Biology (16020) Scientific Communication and Education (2097) Synthetic Biology (4572) Systems Biology (10251) Zoology (2393)
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