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

Min Kyung Nam, Ji Hye Han, Ja Young Jang, Si Eun Yun, Goo Young Kim, Seong Man Kang, Hyangshuk Rhim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2497-2505
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1850
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

Keywords

  • Alpha synuclein
  • Conformation
  • Epitope
  • Subcellular localization

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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