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Cell Rep. 2016 Apr 5;15(1):117-131. doi: 10.1016/j.celrep.2016.03.005. Epub 2016 Mar 24.

PRRT2 Is a Key Component of the Ca(2+)-Dependent Neurotransmitter Release Machinery.

Author information

1
Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
2
Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy.
3
San Raffaele Scientific Institute and Vita Salute University, Via Olgettina 58, 20132 Milano, Italy.
4
Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy.
5
Department of Neuroscience, Istituto Giannina Gaslini, Via Gerolamo Gaslini, 5, 16148 Genova, Italy.
6
Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy. Electronic address: fabio.benfenati@iit.it.

Abstract

Heterozygous mutations in proline-rich transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders, including epilepsy, kinesigenic dyskinesia, and migraine. Most of the mutations lead to impaired PRRT2 expression, suggesting that loss of PRRT2 function may contribute to pathogenesis. We show that PRRT2 is enriched in presynaptic terminals and that its silencing decreases the number of synapses and increases the number of docked synaptic vesicles at rest. PRRT2-silenced neurons exhibit a severe impairment of synchronous release, attributable to a sharp decrease in release probability and Ca(2+) sensitivity and associated with a marked increase of the asynchronous/synchronous release ratio. PRRT2 interacts with the synaptic proteins SNAP-25 and synaptotagmin 1/2. The results indicate that PRRT2 is intimately connected with the Ca(2+)-sensing machinery and that it plays an important role in the final steps of neurotransmitter release.

KEYWORDS:

PRRT2; knockdown; release probability; synaptic transmission; synaptotagmin; synchronous and asynchronous release

PMID:
27052163
PMCID:
PMC4826441
DOI:
10.1016/j.celrep.2016.03.005
[Indexed for MEDLINE]
Free PMC Article

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