PRRT2: from Paroxysmal Disorders to Regulation of Synaptic Function.
In the past few years, proline-rich transmembrane protein (PRRT)2 has been identified as the causative gene for several paroxysmal neurological disorders. Recently, an important role of PRRT2 in synapse development and function has emerged. Knock down of the protein strongly impairs the formation of synaptic contacts and neurotransmitter release. At the nerve terminal, PRRT2 endows synaptic vesicle exocytosis with Ca2+sensitivity by interacting with proteins of the fusion complex and with the Ca2+sensors synaptotagmins (Syts). In the postsynaptic compartment, PRRT2 interacts with glutamate receptors. The study of PRRT2 and of its mutations may help in refining our knowledge of the process of synaptic transmission and elucidating the pathogenetic mechanisms leading to derangement of network function in paroxysmal disorders.
San Raffaele Scientific Institute and Vita Salute University, Via Olgettina 58, 20132 Milano, Italy. Electronic address: valtorta.flavia@hsr.it.
Flavia
F
Valtorta
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, Genova, Italy.
Fabio
F
Benfenati
Department of Neuroscience, Istituto Giannina Gaslini, Via Gerolamo Gaslini, 5, 16148 Genova, Italy.
Federico
F
Zara
San Raffaele Scientific Institute and Vita Salute University, Via Olgettina 58, 20132 Milano, Italy.
Jacopo
J
Meldolesi
D000818:Animals; D005089:Exocytosis / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D009435:Synaptic Transmission / Q000235:genetics*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human; C000609581:PRRT2 protein, mouse
dyskinesia; epilepsy; neuronal development; synaptic transmission; synaptopathies