1. PRRT2 Is a Key Component of the Ca(2+)-Dependent Neurotransmitter Release Machinery.
- Author
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Valente P, Castroflorio E, Rossi P, Fadda M, Sterlini B, Cervigni RI, Prestigio C, Giovedì S, Onofri F, Mura E, Guarnieri FC, Marte A, Orlando M, Zara F, Fassio A, Valtorta F, Baldelli P, Corradi A, and Benfenati F
- Subjects
- Animals, Cells, Cultured, Hippocampus cytology, Hippocampus metabolism, Mice, Mice, Inbred C57BL, Presynaptic Terminals physiology, Rats, Rats, Sprague-Dawley, Synaptic Potentials, Synaptic Vesicles metabolism, Synaptosomal-Associated Protein 25 metabolism, Synaptotagmins metabolism, Calcium Signaling, Exocytosis, Membrane Proteins metabolism, Neurotransmitter Agents metabolism, Presynaptic Terminals metabolism
- 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., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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