Synphilin-1 Is Developmentally Localized to Synaptic Terminals, and Its Association with Synaptic Vesicles Is Modulated by α-Synuclein

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 w...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-06, Vol.277 (26), p.23927-23933
Main Authors: Ribeiro, Cátia S., Carneiro, Katia, Ross, Christopher A., Menezes, João R.L., Engelender, Simone
Format: Article
Language:English
Subjects:
alpha-Synuclein
Animals
Carrier Proteins - analysis
Carrier Proteins - physiology
Nerve Tissue Proteins - analysis
Nerve Tissue Proteins - physiology
Presynaptic Terminals - chemistry
Rats
Rats, Wistar
Synaptic Vesicles - chemistry
Synucleins
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M201115200