Intravesicular localization and exocytosis of α-synuclein and its aggregates

He Jin Lee, Smita Patel, Seung-Jae Lee

Research output: Contribution to journalArticle

483 Citations (Scopus)

Abstract

α-Synuclein (α-syn), particularly in its aggregated forms, is implicated in the pathogenesis of Parkinson's disease and other related neurological disorders. However, the normal biology of α-syn and how it relates to the aggregation of the protein are not clearly understood. Because of the lack of the signal sequence and its predominant localization in the cytosol, α-syn is generally considered exclusively an intracellular protein. Contrary to this assumption, here, we show that a small percentage of newly synthesized α-syn is rapidly secreted from cells via unconventional, endoplasmic reticulum/Golgi-independent exocytosis. Consistent with this finding, we also demonstrate that a portion of cellular α-syn is present in the lumen of vesicles. Importantly, the intravesicular α-syn is more prone to aggregation than the cytosolic protein, and aggregated forms of α-syn are also secreted from cells. Furthermore, secretion of both monomeric and aggregated α-syn is elevated in response to proteasomal and mitochondrial dysfunction, cellular defects that are associated with Parkinson's pathogenesis. Thus, intravesicular localization and secretion are part of normal life cycle of α-syn and might also contribute to pathological function of this protein.

Original languageEnglish
Pages (from-to)6016-6024
Number of pages9
JournalJournal of Neuroscience
Volume25
Issue number25
DOIs
StatePublished - 22 Jul 2005

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Synucleins
Exocytosis
Proteins
Protein Sorting Signals
Life Cycle Stages
Nervous System Diseases
Endoplasmic Reticulum
Cytosol
Parkinson Disease

Keywords

  • Exocytosis
  • Neurodegeneration
  • Parkinson's disease
  • Protein aggregation
  • Synuclein
  • Vesicle

Cite this

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Intravesicular localization and exocytosis of α-synuclein and its aggregates. / Lee, He Jin; Patel, Smita; Lee, Seung-Jae.

In: Journal of Neuroscience, Vol. 25, No. 25, 22.07.2005, p. 6016-6024.

Research output: Contribution to journalArticle

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