Synphilin-1 is developmentally localized to synaptic terminals, and its association with synaptic vesicles is modulated by alpha-synuclein.
Alpha-synuclein is the major component of Lewy bodies in patients with Parkinson's disease, and mutations in the alpha-synuclein gene are responsible for some familial forms of the disease. alpha-Synuclein is enriched in the presynapse, but its synaptic targets are unknown. Synphilin-1 associates in vivo with alpha-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 alpha-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 alpha-synuclein in the incubation medium. Our data indicated that synphilin-1 is a synaptic partner of alpha-synuclein, and it may mediate synaptic roles attributed to alpha-synuclein.
Ribeiro
Cátia S
CS
Department of Anatomy, Federal University of Rio de Janeiro, Rio de Janeiro 21491-590, Brazil.
Carneiro
Katia
K
Ross
Christopher A
CA
Menezes
João R L
JR
Engelender
Simone
S
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000502:physiology*; D017729:Presynaptic Terminals / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000737:chemistry*; D051843:Synucleins; D051844:alpha-Synuclein
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C497606:Snca protein, rat; C498463:Sncaip protein, rat; D051843:Synucleins; D051844:alpha-Synuclein