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Updated: Feb 22, 2026
10:52
Efficient and Scalable Production of Full-length Human Huntingtin Variants in Mammalian Cells using a Transient Expression System
Published on: December 10, 2021
3.1K
Huntingtin Fibrils Poke Membranes
Pedro Guedes-Dias1, Erika L F Holzbaur1
1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
Cell
|September 23, 2017
Summary
Huntington's disease aggregates have a fibrillary structure that interacts with the endoplasmic reticulum. This interaction distorts the endoplasmic reticulum's shape and function, offering new insights into the disease.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Huntington's disease is characterized by intracellular aggregates of mutant huntingtin.
- The pathological role of these aggregates has been a long-standing question in the field.
Purpose of the Study:
- To elucidate the in situ structure of mutant huntingtin aggregates.
- To investigate the interaction between huntingtin aggregates and cellular organelles, specifically the endoplasmic reticulum.
Main Methods:
- Cryo-electron tomography was employed to visualize the aggregates at high resolution.
- In situ structural analysis of huntingtin aggregates within cells.
Main Results:
- The study revealed the fibrillary nature of huntingtin aggregates.
- Huntingtin fibrils were observed to interact directly with the endoplasmic reticulum.
- This interaction led to observable distortions in endoplasmic reticulum morphology and dynamics.
Conclusions:
- Mutant huntingtin aggregates possess a defined fibrillary structure.
- The interaction of these fibrils with the endoplasmic reticulum contributes to cellular dysfunction in Huntington's disease.
- These findings provide a mechanistic link between aggregate formation and endoplasmic reticulum pathology.
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