Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by α-synuclein

Cátia S. Ribeiro, Katia Carneiro, Christopher A Ross, João R L Menezes, Simone Engelender

Research output: Contribution to journalArticle

Abstract

α-Synuclein is the major component of Lewy bodies in patients with Parkinson's disease, and mutations in the α-synuclein gene are responsible for some familial forms of the disease. α-Synuclein is enriched in the presynapse, but its synaptic targets are unknown. Synphilin-1 associates in vivo with α-synuclein promoting the formation of intracellular inclusions. Additionally synphilin-1 has been found to be an intrinsic component of Lewy bodies in patients with Parkinson's disease. To understand the role of synphilin-1 in Parkinson's disease, we sought to define its localization and function in the brain. We now report that, like α-synuclein, synphilin-1 was enriched in neurons. In young rats, synphilin-1 was prominent in neuronal cell bodies but gradually migrated to neuropil during development. Immunoelectron microscopy of adult rat cerebral cortex demonstrated that synphilin-1 was highly enriched in presynaptic nerve terminals. Synphilin-1 co-immunoprecipitated with synaptic vesicles, indicating a strong association with these structures. In vitro binding experiments demonstrated that the N terminus of synphilin-1 robustly associated with synaptic vesicles and that this association was resistant to high salt washing but was abolished by inclusion of α-synuclein in the incubation medium. Our data indicated that synphilin-1 is a synaptic partner of α-synuclein, and it may mediate synaptic roles attributed to α-synuclein.

Original languageEnglish (US)
Pages (from-to)23927-23933
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number26
DOIs
StatePublished - Jun 28 2002
Externally publishedYes

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Synucleins
Synaptic Vesicles
Presynaptic Terminals
Parkinson Disease
Lewy Bodies
Rats
Neuropil
Immunoelectron Microscopy
Washing
Cerebral Cortex
Neurons
Brain
Microscopic examination
Salts
Genes
Cells
Mutation

ASJC Scopus subject areas

  • Biochemistry

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Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by α-synuclein. / Ribeiro, Cátia S.; Carneiro, Katia; Ross, Christopher A; Menezes, João R L; Engelender, Simone.

In: Journal of Biological Chemistry, Vol. 277, No. 26, 28.06.2002, p. 23927-23933.

Research output: Contribution to journalArticle

Ribeiro, Cátia S. ; Carneiro, Katia ; Ross, Christopher A ; Menezes, João R L ; Engelender, Simone. / Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by α-synuclein. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 26. pp. 23927-23933.
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