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Updated: Jun 9, 2025

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
Published on: February 18, 2014
Intrinsically disordered region amplifies membrane remodeling to augment selective ER-phagy.
Sergio Alejandro Poveda-Cuevas1,2, Kateryna Lohachova1,2, Borna Markusic1,3
1Goethe University Frankfurt, School of Medicine, Institute of Biochemistry II, Frankfurt am Main 60590, Germany.
Intrinsically disordered regions (IDRs) of the ER-phagy receptor FAM134B remodel membranes. These IDRs induce curvature and enhance protein clustering, amplifying ER remodeling functions.
Area of Science:
- Cell Biology
- Biophysics
Background:
- Intrinsically disordered regions (IDRs) are crucial for organelle remodeling, signaling, and transport.
- The endoplasmic reticulum (ER)-phagy receptor FAM134B contains a C-terminal IDR whose function beyond autophagy engagement is unknown.
Purpose of the Study:
- To investigate the structural and functional characteristics of the FAM134B IDR.
- To elucidate the role of FAM134B IDR in membrane remodeling and ER-phagy.
Main Methods:
- Extensive molecular modeling and molecular dynamics simulations.
- Analysis of conformational landscapes in solution and membrane-anchored states.
- Mapping of charge patterns and curvature sensing capabilities.
Main Results:
- FAM134B IDRs exhibit Janus-like membrane interactions, collapsing onto membranes and inducing positive curvature.
- IDRs alone can sense membrane curvature, a conserved trait among ER-phagy receptors.
- Combined with the reticulon homology domain (RHD), IDRs intensify membrane remodeling, protein clustering, and budding efficiency.
Conclusions:
- The FAM134B IDR plays a significant role in modulating ER membrane remodeling through direct membrane interactions.
- IDRs act as key regulators, amplifying the functions of ER-phagy receptors in large-scale ER remodeling.
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