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Updated: Sep 15, 2025

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
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Membralin Selects Foreign Glycoproteins from the Endoplasmic Reticulum to Lysosomes for Degradation

Yong-Hui Zheng1, Jing Zhang2, Xiaoran Lu2

  • 1University of Illinois Chicago.

Research Square
|July 18, 2025
PubMed

Insights

Membralin initiates ER-phagy to degrade viral glycoproteins, a key part of cell-autonomous immunity. This process targets viral proteins, not cellular ones, maintaining homeostasis.

Area of Science:

  • Cellular Biology
  • Immunology
  • Virology

Background:

  • The endoplasmic reticulum (ER) is crucial for protein synthesis and folding.
  • ER-associated degradation (ERAD) pathways clear misfolded proteins.
  • Membralin is a multi-pass membrane protein implicated in ERAD.

Purpose of the Study:

  • To elucidate the role of Membralin in degrading viral glycoproteins.
  • To understand the mechanism of Membralin-mediated protein clearance.
  • To investigate Membralin's contribution to cellular immunity.

Main Methods:

  • Investigated Membralin interactions with MAN1B1 and p97/VCP.
  • Identified the LC3-interacting region (LIR) in Membralin.
  • Analyzed the degradation of viral glycoproteins induced by ER stress.

Main Results:

  • Membralin assembles a degradation machinery targeting viral fusion proteins across the ER membrane.
  • Membralin interacts with MAN1B1 and p97/VCP via its luminal and cytoplasmic loops.
  • Membralin utilizes its LIR to recruit p97/VCP, initiating ER-phagy for viral glycoprotein degradation.
  • The pathway selectively targets dense N-glycans and spares misfolded endogenous proteins.

Conclusions:

  • Membralin orchestrates a cell-autonomous ER immunity against foreign glycoproteins.
  • This pathway is crucial for clearing viral glycoproteins and maintaining cellular homeostasis.
  • Membralin acts as a selective sensor and effector in ER-associated degradation.
Keywords:
ERLADMAN1B1MembralinTMEM259class I fusion proteinsreticulophagy

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