Article
- The EMBO Journal (2004) 23, 4506 - 4516
- doi:10.1038/sj.emboj.7600451
Published online: 28 October 2004
Subject Category:
-Synuclein produces a long-lasting increase in neurotransmitter release
Shumin Liu1,a, Ipe Ninan1,a, Irina Antonova2, Fortunato Battaglia2, Fabrizio Trinchese1, Archana Narasanna1, Nikolai Kolodilov3, William Dauer3, Robert D Hawkins2,4 and Ottavio Arancio1
- Department of Pathology, Columbia University, New York, NY, USA
- Center for Neurobiology and Behavior, Columbia University, New York, NY, USA
- Department of Neurology, Columbia University, New York, NY, USA
- NYSPI, Columbia University, New York, NY, USA
Correspondence to:
Ottavio Arancio, Department of Pathology, Columbia University, 630W 168th St, New York, NY 10032, USA. Tel.: +1 212 342 5527; E-mail: oa1@columbia.edu
aThese authors contributed equally to this work
Received 20 September 2004; Accepted 27 September 2004
Abstract
Wild-type 
-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 -synuclein clusters. Conversely, suppression of -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, -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 -synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of -synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of -synuclein clusters. Thus, -synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal.
Keywords:
- plasticity,
- synapse,
- synuclein,
- terminal
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