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Elife. 2016 Feb 12;5. pii: e12637. doi: 10.7554/eLife.12637.

Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function.

Author information

1
Vollum Institute, Oregon Health and Science University, Portland, United States.
2
Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
3
Institute of Physiology, University of Freiburg, Freiburg, Germany.
4
Center for Biological Signalling Studies (BIOSS), Freiburg, Germany.
5
Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
6
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, United States.

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.

KEYWORDS:

mouse; neuroscience; synaptic plasticity; synaptic scaffold; synaptic transmission

PMID:
26880549
PMCID:
PMC4764564
DOI:
10.7554/eLife.12637
[Indexed for MEDLINE]
Free PMC Article

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