Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function
Gukhan Kim,
Rafael Luján,
Jochen Schwenk,
Melissa H Kelley,
Carolina Aguado,
Masahiko Watanabe,
Bernd Fakler,
James Maylie,
John P Adelman
Affiliations
Gukhan Kim
Vollum Institute, Oregon Health and Science University, Portland, United States
Rafael Luján
Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain
Jochen Schwenk
Institute of Physiology, University of Freiburg, Freiburg, Germany; Center for Biological Signalling Studies (BIOSS), Freiburg, Germany
Melissa H Kelley
Vollum Institute, Oregon Health and Science University, Portland, United States
Carolina Aguado
Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain
Masahiko Watanabe
Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
Bernd Fakler
Institute of Physiology, University of Freiburg, Freiburg, Germany; Center for Biological Signalling Studies (BIOSS), Freiburg, Germany
James Maylie
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, United States
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 Ca2+ 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.
