Your browser doesn't support javascript.
loading
An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABAA Receptors.
Davenport, Elizabeth C; Pendolino, Valentina; Kontou, Georgina; McGee, Thomas P; Sheehan, David F; López-Doménech, Guillermo; Farrant, Mark; Kittler, Josef T.
Afiliación
  • Davenport EC; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
  • Pendolino V; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
  • Kontou G; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
  • McGee TP; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
  • Sheehan DF; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
  • López-Doménech G; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
  • Farrant M; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: m.farrant@ucl.ac.uk.
  • Kittler JT; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: j.kittler@ucl.ac.uk.
Cell Rep ; 21(1): 70-83, 2017 Oct 03.
Article en En | MEDLINE | ID: mdl-28978485
Inhibitory synaptic transmission requires the targeting and stabilization of GABAA receptors (GABAARs) at synapses. The mechanisms responsible remain poorly understood, and roles for transmembrane accessory proteins have not been established. Using molecular, imaging, and electrophysiological approaches, we identify the tetraspanin LHFPL4 as a critical regulator of postsynaptic GABAAR clustering in hippocampal pyramidal neurons. LHFPL4 interacts tightly with GABAAR subunits and is selectively enriched at inhibitory synapses. In LHFPL4 knockout mice, there is a dramatic cell-type-specific reduction in GABAAR and gephyrin clusters and an accumulation of large intracellular gephyrin aggregates in vivo. While GABAARs are still trafficked to the neuronal surface in pyramidal neurons, they are no longer localized at synapses, resulting in a profound loss of fast inhibitory postsynaptic currents. Hippocampal interneuron currents remain unaffected. Our results establish LHFPL4 as a synapse-specific tetraspanin essential for inhibitory synapse function and provide fresh insights into the molecular make-up of inhibitory synapses.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Proteínas Portadoras / Receptores de GABA-A / Subunidades de Proteína / Potenciales Postsinápticos Inhibidores / Tetraspaninas / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Proteínas Portadoras / Receptores de GABA-A / Subunidades de Proteína / Potenciales Postsinápticos Inhibidores / Tetraspaninas / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos