title: Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function.
abstract: Mouse CA1 pyramidal neurons express apamin-sensitive SK2-containing channels in the post-synaptic membrane, positioned close to NMDA-type (N-methyl-D-aspartate) glutamate receptors. Activated by synaptically evoked NMDAR-dependent Ca(2+) influx, the synaptic SK2-containing channels modulate excitatory post-synaptic responses and the induction of synaptic plasticity. In addition, their activity- and protein kinase A-dependent trafficking contributes to expression of long-term potentiation (LTP). We have identified a novel synaptic scaffold, MPP2 (membrane palmitoylated protein 2; p55), a member of the membrane-associated guanylate kinase (MAGUK) family that interacts with SK2-containing channels. MPP2 and SK2 co-immunopurified from mouse brain, and co-immunoprecipitated when they were co-expressed in HEK293 cells. MPP2 is highly expressed in the post-synaptic density of dendritic spines on CA1 pyramidal neurons. Knocking down MPP2 expression selectively abolished the SK2-containing channel contribution to synaptic responses and decreased LTP. Thus, MPP2 is a novel synaptic scaffold that is required for proper synaptic localization and function of SK2-containing channels.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, United States.
authors.forename: Gukhan
authors.initials: G
authors.lastname: Kim
authors.affiliation: Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
authors.affiliation: Institute of Physiology, University of Freiburg, Freiburg, Germany.|Center for Biological Signalling Studies (BIOSS), Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schwenk
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, United States.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Kelley
authors.affiliation: Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Aguado
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Institute of Physiology, University of Freiburg, Freiburg, Germany.|Center for Biological Signalling Studies (BIOSS), Freiburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
authors.affiliation: Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, United States.
authors.forename: James
authors.initials: J
authors.lastname: Maylie
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, United States.
authors.forename: John P
authors.identifier: http://orcid.org/0000-0002-1135-1549
authors.initials: JP
authors.lastname: Adelman
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D002460:Cell Line; D051528:Guanylate Kinases / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D017966:Pyramidal Cells / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: C496898:Kcnn2 protein, mouse; D008565:Membrane Proteins; D051640:Small-Conductance Calcium-Activated Potassium Channels; C501445:Dlg2 protein, mouse; D051528:Guanylate Kinases
keywords: mouse; neuroscience; synaptic plasticity; synaptic scaffold; synaptic transmission