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PRRT2 modulates presynaptic Ca2+ influx by interacting with P/Q-type channels.
Ferrante, Daniele; Sterlini, Bruno; Prestigio, Cosimo; Marte, Antonella; Corradi, Anna; Onofri, Franco; Tortarolo, Giorgio; Vicidomini, Giuseppe; Petretto, Andrea; Muià, Jessica; Thalhammer, Agnes; Valente, Pierluigi; Cingolani, Lorenzo A; Benfenati, Fabio; Baldelli, Pietro.
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  • Ferrante D; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
  • Sterlini B; 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.
  • Prestigio C; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
  • Marte A; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; IRCCS, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
  • Corradi A; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; IRCCS, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
  • Onofri F; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; IRCCS, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
  • Tortarolo G; Molecular Microscopy and Spectroscopy, Istituto Italiano di Tecnologia, Via Enrico Melen, 83B, 16152, Genova, Italy.
  • Vicidomini G; Molecular Microscopy and Spectroscopy, Istituto Italiano di Tecnologia, Via Enrico Melen, 83B, 16152, Genova, Italy.
  • Petretto A; Core Facilities-Clinical Proteomics and Metabolomics, IRCCS, Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy.
  • Muià J; 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.
  • Thalhammer A; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy.
  • Valente P; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; IRCCS, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.
  • Cingolani LA; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy; Department of Life Sciences, University of Trieste, Trieste, Italy.
  • Benfenati F; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy; IRCCS, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy. Electronic address: fabio.benfenati@iit.it.
  • Baldelli P; Department of Experimental Medicine, University of Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; IRCCS, Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy. Electronic address: pietro.baldelli@unige.it.
Cell Rep ; 35(11): 109248, 2021 06 15.
Article en En | MEDLINE | ID: mdl-34133925
Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca2+ dependence of glutamatergic transmission. We find that either acute or constitutive PRRT2 deletion induces a significant decrease in the amplitude of evoked excitatory postsynaptic currents (eEPSCs) that is insensitive to extracellular Ca2+ and associated with a reduced contribution of P/Q-type Ca2+ channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca2+ currents due to a decreased membrane targeting of the channel with unchanged total expression levels. Co-immunoprecipitation, pull-down assays, and proteomics reveal a specific and direct interaction of PRRT2 with P/Q-type Ca2+ channels. At presynaptic terminals lacking PRRT2, P/Q-type Ca2+ channels reduce their clustering at the active zone, with a corresponding decrease in the P/Q-dependent presynaptic Ca2+ signal. The data highlight the central role of PRRT2 in ensuring the physiological Ca2+ sensitivity of the release machinery at glutamatergic synapses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Calcio / Calcio / Terminales Presinápticos / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Calcio / Calcio / Terminales Presinápticos / Proteínas de la Membrana Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos