title: Coassembly and coupling of SK2 channels and mGlu5 receptors.
abstract: Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca(2+) wave-dependent activation of small-conductance Ca(2+)-activated K(+) (SK) channels. Here, we show that mGlu5 receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu5 receptor stimulation activated apamin-sensitive SK2-mediated K(+) currents. In addition, coexpression of mGlu5 receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu5 receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu5 receptors and SK2 channels that reflects their molecular coassembly.
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
authors.forename: Gloria
authors.initials: G
authors.lastname: García-Negredo
authors.affiliation: Laboratori de Neurobiologia, Institut d'Investigacions Biomèdiques de Bellvitge, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Soto
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
authors.forename: Javier
authors.initials: J
authors.lastname: Llorente
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
authors.forename: Xavier
authors.initials: X
authors.lastname: Morató
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
authors.forename: Koen M O
authors.initials: KM
authors.lastname: Galenkamp
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
authors.forename: Maricel
authors.initials: M
authors.lastname: Gómez-Soler
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
authors.forename: Víctor
authors.initials: V
authors.lastname: Fernández-Dueñas
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-0818, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, Rafael.Lujan@uclm.es adelman@ohsu.edu fciruela@ub.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Adelman
authors.affiliation: Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, and.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.affiliation: Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, and.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Fukazawa
authors.affiliation: Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, 02008 Albacete, Spain Rafael.Lujan@uclm.es adelman@ohsu.edu fciruela@ub.edu.
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, Rafael.Lujan@uclm.es adelman@ohsu.edu fciruela@ub.edu.
authors.forename: Francisco
authors.identifier: http://orcid.org/0000-0003-0832-3739
authors.initials: F
authors.lastname: Ciruela
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D002118:Calcium
keywords: SK2 channel; apamin; electron microscopy; mGlu5 receptor; oligomerization