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

doi:10.1073/pnas.0406283101

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

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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, …

Proceedings of the National Academy of Sciences - PNAS, Vol.101(41), pp.14966-14971

10/12/2004

DOI: 10.1073/pnas.0406283101

PMCID: PMC522043

PMID: 15465911

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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-deficient 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.

Biological Sciences

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Title: Subtitle: Double-knockout mice for α- and β-synucleins: Effect on synaptic functions
Creators: Sreeganga Chandra - Center for Basic Neuroscience, Departments of
Francesco Fornai - Center for Basic Neuroscience, Departments of
Hyung-Bae Kwon - Center for Basic Neuroscience, Departments of
Umar Yazdani - Center for Basic Neuroscience, Departments of
Deniz Atasoy - Center for Basic Neuroscience, Departments of
Xinran Liu - Center for Basic Neuroscience, Departments of
Robert E Hammer - Center for Basic Neuroscience, Departments of
Giuseppe Battaglia - Center for Basic Neuroscience, Departments of
Dwight C German - Center for Basic Neuroscience, Departments of
Pablo E Castillo - Center for Basic Neuroscience, Departments of
Thomas C Südhof - Center for Basic Neuroscience, Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.101(41), pp.14966-14971
DOI: 10.1073/pnas.0406283101
PMID: 15465911
PMCID: PMC522043
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 10/12/2004
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984040012402771

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