Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/12637 |
| _version_ | 1811253413194760192 |
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| author | Gukhan Kim Rafael Luján Jochen Schwenk Melissa H Kelley Carolina Aguado Masahiko Watanabe Bernd Fakler James Maylie John P Adelman |
| author_facet | Gukhan Kim Rafael Luján Jochen Schwenk Melissa H Kelley Carolina Aguado Masahiko Watanabe Bernd Fakler James Maylie John P Adelman |
| author_sort | Gukhan Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:50:32Z |
| format | Article |
| id | doaj.art-27fe61ee549d445eb1c0bd9a967061c0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:50:32Z |
| publishDate | 2016-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-27fe61ee549d445eb1c0bd9a967061c02022-12-22T03:24:24ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.12637Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel functionGukhan Kim0Rafael Luján1Jochen Schwenk2Melissa H Kelley3Carolina Aguado4Masahiko Watanabe5Bernd Fakler6James Maylie7John P Adelman8https://orcid.org/0000-0002-1135-1549Vollum Institute, Oregon Health and Science University, Portland, United StatesInstituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, SpainInstitute of Physiology, University of Freiburg, Freiburg, Germany; Center for Biological Signalling Studies (BIOSS), Freiburg, GermanyVollum Institute, Oregon Health and Science University, Portland, United StatesInstituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, SpainDepartment of Anatomy, Hokkaido University School of Medicine, Sapporo, JapanInstitute of Physiology, University of Freiburg, Freiburg, Germany; Center for Biological Signalling Studies (BIOSS), Freiburg, GermanyDepartment of Obstetrics and Gynecology, Oregon Health and Science University, Portland, United StatesVollum Institute, Oregon Health and Science University, Portland, United StatesMouse 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.https://elifesciences.org/articles/12637synaptic transmissionsynaptic plasticitysynaptic scaffold |
| spellingShingle | Gukhan Kim Rafael Luján Jochen Schwenk Melissa H Kelley Carolina Aguado Masahiko Watanabe Bernd Fakler James Maylie John P Adelman Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function eLife synaptic transmission synaptic plasticity synaptic scaffold |
| title | Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function |
| title_full | Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function |
| title_fullStr | Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function |
| title_full_unstemmed | Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function |
| title_short | Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function |
| title_sort | membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic sk2 containing channel function |
| topic | synaptic transmission synaptic plasticity synaptic scaffold |
| url | https://elifesciences.org/articles/12637 |
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