α-Synuclein multimers cluster synaptic vesicles and attenuate recycling

Lina Wang, Utpal Das, David A. Scott, Yong Tang, Pamela J McLean, Subhojit Roy

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

The normal functions and pathologic facets of the small presynaptic protein α-synuclein (α-syn) are of exceptional interest. In previous studies, we found that α-syn attenuates synaptic exo/endocytosis [1, 2]; however, underlying mechanisms remain unknown. More recent evidence suggests that α-syn exists as metastable multimers and not solely as a natively unfolded monomer [3-8]. However, conformations of α-syn at synapses - its physiologic locale - are unclear, and potential implications of such higher-order conformations to synaptic function are unknown. Exploring α-syn conformations and synaptic function in neurons, we found that α-syn promptly organizes into physiological multimers at synapses. Furthermore, our experiments indicate that α-syn multimers cluster synaptic vesicles and restrict their motility, suggesting a novel role for these higher-order structures. Supporting this, α-syn mutations that disrupt multimerization also fail to restrict synaptic vesicle motility or attenuate exo/endocytosis. We propose a model in which α-syn multimers cluster synaptic vesicles, restricting their trafficking and recycling, and consequently attenuate neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)2319-2326
Number of pages8
JournalCurrent Biology
Volume24
Issue number19
DOIs
StatePublished - Oct 6 2014

Fingerprint

Synucleins
Synaptic Vesicles
Recycling
recycling
Conformations
endocytosis
synapse
Endocytosis
Synapses
neurotransmitters
Neurons
Neurotransmitter Agents
Monomers
neurons
mutation
Mutation
synaptic vesicles
Proteins
proteins
Experiments

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

α-Synuclein multimers cluster synaptic vesicles and attenuate recycling. / Wang, Lina; Das, Utpal; Scott, David A.; Tang, Yong; McLean, Pamela J; Roy, Subhojit.

In: Current Biology, Vol. 24, No. 19, 06.10.2014, p. 2319-2326.

Research output: Contribution to journalArticle

Wang, Lina ; Das, Utpal ; Scott, David A. ; Tang, Yong ; McLean, Pamela J ; Roy, Subhojit. / α-Synuclein multimers cluster synaptic vesicles and attenuate recycling. In: Current Biology. 2014 ; Vol. 24, No. 19. pp. 2319-2326.
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