---
title: "DFCP1 membrane coat forms a diffusion barrier that concentrates PI3P for lysosome repair"
id: "biorxiv-18-structure-and-function-of-the-dfcp1-membrane-barrier-responsible-for-er"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-18-structure-and-function-of-the-dfcp1-membrane-barrier-responsible-for-er"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.19.759623v1?rss=1"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# DFCP1 membrane coat forms a diffusion barrier that concentrates PI3P for lysosome repair
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-18-structure-and-function-of-the-dfcp1-membrane-barrier-responsible-for-er
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.19.759623v1?rss=1)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study determined the structure of full-length human **DFCP1** bound to membranes using cryo-electron tomography and single-particle cryo-electron microscopy. The structural work is the source of the mechanistic claims. - DFCP1 assembles into a helical coat made from tetramers that stack around a constricted membrane tube, with ATPase domains forming the helix core and ER-targeting domains inserting into the outer leaflet. - FYVE domains of DFCP1 bind **PI3P**, and simulations indicate the coat impedes lateral lipid movement, concentrating **PI3P** beneath the filament rather than allowing free diffusion across it. - Coarse-grained molecular dynamics simulations were used to model lipid diffusion relative to the coat and showed near-complete blockade of the cognate lipid’s movement past the filament in silico. - Point mutations that disrupt assembly interfaces, membrane insertion, or **PI3P** binding each impaired lysosomal repair in cellular assays, according to the authors’ report. - The assembly is required for focal recruitment of the lipid transporter **VPS13C**; mutation of DFCP1 interfaces disrupted this recruitment in cells. - The authors propose that DFCP1 collars create a fenced ER microdomain so that locally synthesized lipids can be delivered to lysosomal repair sites rather than diffusing into bulk ER. - The source did not report quantitative kinetics, exact mutation sequences, nor detailed cellular assay conditions in the abstract; those specifics are not available in the text provided. - Competing interest: one author holds shares in a biotech company; all other authors declared no competing interests. Funding included Aligning Science Across Parkinson’s (ASAP).
## Clinical Analysis & Structured Key Points
Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair | bioRxiv Skip to main content New Results Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair View ORCID Profile Zhicheng Cui , View ORCID Profile Karen Palacio-Rodriguez , View ORCID Profile Eric Herrmann , View ORCID Profile Athanasios Kourniotis , View ORCID Profile Maja Radulovic , View ORCID Profile Sascha Pust , View ORCID Profile Karla Tapia , View ORCID Profile Camilla Raiborg , View ORCID Profile Gerhard Hummer , View ORCID Profile Harald Stenmark , View ORCID Profile James H Hurley doi: https://doi.org/10.64898/2026.10.19.759623 Zhicheng Cui 1 University of Colorado; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Zhicheng Cui Karen Palacio-Rodriguez 2 Max Planck Institute for Biophysics; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Karen Palacio-Rodriguez Eric Herrmann 3 UC Berkeley; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Eric Herrmann Athanasios Kourniotis 4 University of Oslo; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Athanasios Kourniotis Maja Radulovic 4 University of Oslo; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Maja Radulovic Sascha Pust 5 Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sascha Pust Karla Tapia 1 University of Colorado; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Karla Tapia Camilla Raiborg 6 Oslo University Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Camilla Raiborg Gerhard Hummer 7 Max Planck Institute of Biophysics Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gerhard Hummer Harald Stenmark 6 Oslo University Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Harald Stenmark James H Hurley 3 UC Berkeley; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for James H Hurley For correspondence: jimhurley{at}berkeley.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract The endoplasmic reticulum (ER) forms specialized microdomains that organize autophagy, lipid droplet formation, and the repair of damaged lysosomes. The PI3P-binding protein DFCP1/ZFYVE1 marks these microdomains, raising the question as to whether and how one protein could define such a subcompartment. Here we determine the structure of full-length human DFCP1 bound to membranes by cryo-electron tomography and single-particle cryo-electron microscopy. DFCP1 assembles into a helical coat, built from tetramers that stack around a constricted membrane tube. Its ATPase domains form the organizing core of the helix, while its ER-targeting domains insert deeply into the outer leaflet, and its FYVE domains grip PI3P. Coarse-grained molecular dynamics simulations show that the coat does not simply follow the curvature of the membrane but acts as a barrier to lipid diffusion, almost completely blocking the movement of its cognate lipid PI3P past the filament and concentrating it beneath the coat. Point mutations that break the assembly, membrane-insertion or PI3P-binding interfaces each impair lysosomal repair in cells, and the assembly is also required for the focal recruitment of the lipid transporter VPS13C. We propose that DFCP1 collars fence off a specialized ER microdomain, so that locally made lipids can reach sites of repair rather than escaping into bulk ER. Competing Interest Statement J.H.H. is a shareholder of Casma Therapeutics. The other authors declare no competing interests. Funder Information Declared Aligning Science Across Parkinson's , ASAP-000350 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 October 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. You are going to email the following Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair Zhicheng Cui , Karen Palacio-Rodriguez , Eric Herrmann , Athanasios Kourniotis , Maja Radulovic , Sascha Pust , Karla Tapia , Camilla Raiborg , Gerhard Hummer , Harald Stenmark , James H Hurley bioRxiv 2026.10.19.759623; doi: https://doi.org/10.64898/2026.10.19.759623 Share This Article: Copy Citation Tools Structure and function of the DFCP1 membrane barrier responsible for ER microdomain organization in lysosome repair Zhicheng Cui , Karen Palacio-Rodriguez , Eric Herrmann , Athanasios Kourniotis , Maja Radulovic , Sascha Pust , Karla Tapia , Camilla Raiborg , Gerhard Hummer , Harald Stenmark , James H Hurley bioRxiv 2026.10.19.759623; doi: https://doi.org/10.64898/2026.10.19.759623 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 Area Cell Biology Subject Areas All Articles Animal Behavior and Cognition (8164) Biochemistry (19027) Bioengineering (15171) Bioinformatics (45329) Biophysics (22958) Cancer Biology (20111) Cell Biology (27298) Clinical Trials (138) Developmental Biology (14143) Ecology (21395) Epidemiology (2067) Evolutionary Biology (25783) Genetics (16342) Genomics (23828) Immunology (19018) Microbiology (43184) Molecular Biology (18339) Neuroscience (95055) Paleontology (712) Pathology (3032) Pharmacology and Toxicology (5198) Physiology (8280) Plant Biology (16270) Scientific Communication and Education (2115) Synthetic Biology (4644) Systems Biology (10384) Zoology (2426)
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