Double-knockout mice for α- and β-synucleins: Effect on synaptic functions

Sreeganga Chandra, Francesco Fornai, Hyung Bae Kwon, Umar Yazdani, Deniz Atasoy, Xinran Liu, Robert E. Hammer, Giuseppe Battaglia, Dwight C. German, Pablo E. Castillo, Thomas C. Südhof

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Abstract

An abundant presynaptic protein, α-synuclein, is centrally involved in the pathogenesis of Parkinson's disease. However, conflicting data exist about the normal function of α-synuclein, possibly because α-synuclein is redundant with the very similar β-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack α- and/or β-synuclein. We find that deletion of synucleins in mice does not impair basic brain functions or survival. We detected no significant changes in the ultrastructure of synuclein-cleficient synapses, in short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles. However, protein quantitations revealed that KO of synucleins caused selective changes in two small synaptic signaling proteins, complexins and 14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double-KO but not single-KO mice were decreased by ≈20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function.

Original languageEnglish (US)
Pages (from-to)14966-14971
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number41
DOIs
StatePublished - Oct 12 2004

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    Chandra, S., Fornai, F., Kwon, H. B., Yazdani, U., Atasoy, D., Liu, X., Hammer, R. E., Battaglia, G., German, D. C., Castillo, P. E., & Südhof, T. C. (2004). Double-knockout mice for α- and β-synucleins: Effect on synaptic functions. Proceedings of the National Academy of Sciences of the United States of America, 101(41), 14966-14971. https://doi.org/10.1073/pnas.0406283101