alpha-Synuclein produces a long-lasting increase in neurotransmitter release.
Wild-type alpha-synuclein, a protein of unknown function, has received much attention because of its involvement in a series of diseases that are known as synucleinopathies. We find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of alpha-synuclein clusters. Conversely, suppression of alpha-synuclein expression through antisense nucleotide and knockout techniques blocks the potentiation, as well as the glutamate-induced increase in presynaptic functional bouton number. Consistent with these findings, alpha-synuclein introduction into the presynaptic neuron of a pair of monosynaptically connected cells causes a rapid and long-lasting enhancement of synaptic transmission, and rescues the block of potentiation in alpha-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of alpha-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of alpha-synuclein clusters. Thus, alpha-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal.
Liu
Shumin
S
Department of Pathology, Columbia University, New York, NY, USA.
Ninan
Ipe
I
Antonova
Irina
I
Battaglia
Fortunato
F
Trinchese
Fabrizio
F
Narasanna
Archana
A
Kolodilov
Nikolai
N
Dauer
William
W
Hawkins
Robert D
RD
Arancio
Ottavio
O
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D004594:Electrophysiology; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D051843:Synucleins; D051844:alpha-Synuclein
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; C497605:Snca protein, mouse; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase