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Updated: Apr 3, 2026

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
Published on: May 30, 2021
A novel link between the conformations, exposure of specific epitopes, and subcellular localization of α-synuclein
Min-Kyung Nam1, Ji-Hye Han1, Ja-Young Jang2
1Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea; Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Background:
Genetic studies and the abundance of alpha-synuclein (α-Syn) in presynaptic terminals suggest that α-Syn plays a critical role in maintaining synaptic vesicle pools. However, there are still few experimental tools for elucidating its physiological roles.
Methods:
Unexpectedly, we detected various cellular distribution patterns of endogenous α-Syn by immunofluorescence assays (IFAs). To provide new molecular insights into α-Syn research, we identified associations between epitopes, conformations, and subcellular localization of α-Syn and categorized them.
Results:
The α-Syn exposing Y125 was found to coexist with F-actin at the edge of the cells, including the plasma membrane. α-Syn conformations exposing P128 or both F94 and K97 were partly localized to the mitochondria. These results indicate that various conformations of α-Syn are associated with specific subcellular localizations. Intriguingly, we demonstrate for the first time that the phosphorylated α-Syn at Ser129, also known as a Parkinson's disease (PD)-causing form, is targeted to the mitochondria.
Conclusions:
Our study showed that different subcellular distribution patterns of α-Syn reflect the existence of various α-Syn conformations under normal conditions.
General Significance:
This study provides novel clues for deciphering the physiological function of α-Syn in connection with subcellular localization. Dissecting the specific α-Syn conformations may lead to useful strategies in PD therapy and diagnosis.
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