Related Experiment Video

Updated: Jun 4, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

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Release of FUS into the extracellular space is regulated by its amino-terminal prion-like domain

Tadashi Nakaya1

  • 1School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan.

FEBS Letters
|December 31, 2024
PubMed

Insights

Fused in sarcoma (FUS) protein release from neurons is key to amyotrophic lateral sclerosis (ALS) propagation. This study shows human FUS is released from neurons, driven by its amino-terminal region.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease.
  • Fused in sarcoma (FUS) protein aggregation is implicated in ALS pathogenesis.
  • Cell-to-cell transmission of FUS is a proposed mechanism for ALS progression.

Purpose of the Study:

  • To investigate the mechanism of FUS release from neurons.
  • To identify factors influencing differential release of human vs. mouse FUS.
  • To understand the role of FUS domains in its secretion.

Main Methods:

  • Analysis of human and mouse FUS release from cultured neurons.
  • Utilized chimeric FUS proteins to map functional domains.
  • Quantification of FUS protein in cell media.

Main Results:

  • Human FUS is significantly released from neurons into the extracellular environment.
  • Mouse FUS exhibits substantially lower release compared to human FUS.
  • The amino-terminal region of human FUS was identified as critical for its release.

Conclusions:

  • Human FUS is directly released from neurons, a novel finding in ALS research.
  • The amino-terminal region of FUS plays a crucial role in its secretion.
  • Understanding FUS release mechanisms could offer new therapeutic targets for ALS.
Keywords:
FUSextracellularprion‐like domain

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