Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Regulation of Nuclear Protein Sorting

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...

Tail-anchoring of Proteins in the ER Membrane

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Nuclear export modulates TDP-43 phase transition and cytoplasmic aggregation.

bioRxiv : the preprint server for biology·2026

Same author

CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome.

Nature·2026

Same author

Palmitoyl Acyltransferases Control the Membrane Localization of DNAJC5 to Regulate Unconventional Protein Secretion.

Traffic (Copenhagen, Denmark)·2026

Same author

Association of Marshall CT Scores with GFAP, UCH-L1, Tau, NfL, and p-Tau231 After Traumatic Brain Injury.

International journal of molecular sciences·2025

Same author

Orthosteric Molecular Glue Inhibits COP9 Signalosome with Substrate-Dependent Potency.

bioRxiv : the preprint server for biology·2025

Same author

Cysteine-enabled cleavability to advance cross-linking mass spectrometry for global analysis of endogenous protein-protein interactions.

Nature communications·2025

Search research articles

Related Experiment Video

Updated: May 10, 2025

Microfluidic-based Electrotaxis for On-demand Quantitative Analysis of Caenorhabditis elegans' Locomotion

Microfluidic-based Electrotaxis for On-demand Quantitative Analysis of Caenorhabditis elegans' Locomotion

Published on: May 2, 2013

NEMF-mediated CAT tailing facilitates translocation-associated quality control.

Amanda Ennis¹, Lihui Wang¹, Yue Xu¹

¹Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

The Journal of Cell Biology

|April 21, 2025

Summary

Cells degrade stalled proteins using distinct pathways. Nonstop mRNA-translated proteins are targeted for degradation via a novel ER-associated degradation (ERAD) pathway involving Golgi retrieval and NEMF-mediated tailing.

More Related Videos

Author Spotlight: Advanced Techniques for Visualizing Endogenous Axonal Transport Dynamics

Author Spotlight: Advanced Techniques for Visualizing Endogenous Axonal Transport Dynamics

Published on: February 16, 2024

A Murine Tail Lymphedema Model

A Murine Tail Lymphedema Model

Published on: February 10, 2021

Related Experiment Videos

Last Updated: May 10, 2025

Microfluidic-based Electrotaxis for On-demand Quantitative Analysis of Caenorhabditis elegans' Locomotion

Microfluidic-based Electrotaxis for On-demand Quantitative Analysis of Caenorhabditis elegans' Locomotion

Published on: May 2, 2013

Author Spotlight: Advanced Techniques for Visualizing Endogenous Axonal Transport Dynamics

Author Spotlight: Advanced Techniques for Visualizing Endogenous Axonal Transport Dynamics

Published on: February 16, 2024

A Murine Tail Lymphedema Model

A Murine Tail Lymphedema Model

Published on: February 10, 2021

Area of Science:

Cell Biology
Molecular Biology
Protein Biogenesis

Background:

Ribosome stalling during co-translational translocation at the endoplasmic reticulum (ER) can lead to translocon clogging.
Impaired ER protein biogenesis results from translocon clogging.
Translocation-associated quality control (TAQC) is a poorly understood process that resolves translocon clogging in mammalian cells.

Purpose of the Study:

To elucidate the molecular mechanisms underlying the translocation-associated quality control (TAQC) process.
To differentiate the degradation pathways for various TAQC substrates.
To identify key factors involved in the quality control of nascent protein chains.

Main Methods:

Genome-wide CRISPR screen
Live-cell imaging
Analysis of protein degradation pathways (lysosomal, proteasomal, ERAD)

Main Results:

TAQC substrates from mRNAs with ribosome-stalling poly(A) sequences are degraded by lysosomes and the proteasome.
Defective nascent chains from nonstop (NS) mRNAs are degraded via an unconventional ER-associated protein degradation (ERAD) pathway.
This ERAD pathway involves ER-to-Golgi trafficking, KDEL-mediated retrieval at the Golgi, and the tRNA-binding factor NEMF.
NEMF appends an aggregation-prone carboxyl tail to stalled NS nascent chains, termed CAT tailing.

Conclusions:

NEMF-mediated CAT tailing targets a subset of TAQC substrates for ERAD through Golgi retrieval.
This novel pathway safeguards ER homeostasis by clearing defective nascent chains.
The study reveals distinct degradation routes for TAQC substrates, highlighting the complexity of protein quality control in the ER.