Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions.
An abundant presynaptic protein, alpha-synuclein, is centrally involved in the pathogenesis of Parkinson's disease. However, conflicting data exist about the normal function of alpha-synuclein, possibly because alpha-synuclein is redundant with the very similar beta-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack alpha- and/or beta-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 approximately 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.
Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sreeganga
S
Chandra
Francesco
F
Fornai
Hyung-Bae
HB
Kwon
Umar
U
Yazdani
Deniz
D
Atasoy
Xinran
X
Liu
Robert E
RE
Hammer
Giuseppe
G
Battaglia
Dwight C
DC
German
Pablo E
PE
Castillo
Thomas C
TC
Südhof
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D003342:Corpus Striatum / Q000502:physiology*; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology / Q000648:ultrastructure; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein
D017931:DNA Primers; D009419:Nerve Tissue Proteins; C497605:Snca protein, mouse; C497608:Sncb protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D004298:Dopamine