A novel link between the conformations, exposure of specific epitopes, and subcellular localization of a-synuclein.

Biochimica et biophysica acta

PubMedID: 26391842

Nam MK, Han JH, Jang JY, Yun SE, Kim GY, Kang S, Rhim H. A novel link between the conformations, exposure of specific epitopes, and subcellular localization of a-synuclein. Biochim Biophys Acta. 2015;1850(12):2497-2505.
BACKGROUND
Genetic studies and the abundance of alpha-synuclein (a-Syn) in presynaptic terminals suggest that a-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 a-Syn by immunofluorescence assays (IFAs). To provide new molecular insights into a-Syn research, we identified associations between epitopes, conformations, and subcellular localization of a-Syn and categorized them.

RESULTS
The a-Syn exposing Y125 was found to coexist with F-actin at the edge of the cells, including the plasma membrane. a-Syn conformations exposing P128 or both F94 and K97 were partly localized to the mitochondria. These results indicate that various conformations of a-Syn are associated with specific subcellular localizations. Intriguingly, we demonstrate for the first time that the phosphorylated a-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 a-Syn reflect the existence of various a-Syn conformations under normal conditions.

GENERAL SIGNIFICANCE
This study provides novel clues for deciphering the physiological function of a-Syn in connection with subcellular localization. Dissecting the specific a-Syn conformations may lead to useful strategies in PD therapy and diagnosis.