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

Research output: Contribution to journalArticle

5 Scopus citations

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 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.

Original languageEnglish (US)
Article numbere12637
JournaleLife
Volume5
Issue numberFEBRUARY2016
DOIs
StatePublished - Feb 12 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Kim, G., Luján, R., Schwenk, J., Kelley, M. H., Aguado, C., Watanabe, M., Fakler, B., Maylie, J., & Adelman, J. P. (2016). Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function. eLife, 5(FEBRUARY2016), [e12637]. https://doi.org/10.7554/eLife.12637