Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin
Activity-regulated cytoskeleton-associated protein, Arc, is a major regulator of long-term synaptic plasticity and memory formation. Here we reveal a novel interaction partner of Arc, a resident endoplasmic reticulum transmembrane protein, calnexin. We show an interaction between recombinantly-expre...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00294/full |
| _version_ | 1818299239941275648 |
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| author | Craig Myrum Craig Myrum Jonathan Soulé Margarethe Bittins Kyle Cavagnini Kevin Goff Silje K. Ziemek Maria S. Eriksen Sudarshan Patil Adrian Szum Rajeevkumar R. Nair Clive R. Bramham |
| author_facet | Craig Myrum Craig Myrum Jonathan Soulé Margarethe Bittins Kyle Cavagnini Kevin Goff Silje K. Ziemek Maria S. Eriksen Sudarshan Patil Adrian Szum Rajeevkumar R. Nair Clive R. Bramham |
| author_sort | Craig Myrum |
| collection | DOAJ |
| description | Activity-regulated cytoskeleton-associated protein, Arc, is a major regulator of long-term synaptic plasticity and memory formation. Here we reveal a novel interaction partner of Arc, a resident endoplasmic reticulum transmembrane protein, calnexin. We show an interaction between recombinantly-expressed GST-tagged Arc and endogenous calnexin in HEK293, SH-SY5Y neuroblastoma and PC12 cells. The interaction was dependent on the central linker region of the Arc protein that is also required for endocytosis of AMPA-type glutamate receptors. High-resolution proximity-ligation assays (PLAs) demonstrate molecular proximity of endogenous Arc with the cytosolic C-terminus, but not the lumenal N-terminus of calnexin. In hippocampal neuronal cultures treated with brain-derived neurotrophic factor (BDNF), Arc interacted with calnexin in the perinuclear cytoplasm and dendritic shaft. Arc also interacted with C-terminal calnexin in the adult rat dentate gyrus (DG). After induction of long-term potentiation (LTP) in the perforant path projection to the DG of adult anesthetized rats, enhanced interaction between Arc and calnexin was obtained in the dentate granule cell layer (GCL). Although Arc and calnexin are both implicated in the regulation of receptor endocytosis, no modulation of endocytosis was detected in transferrin uptake assays. Previous work showed that Arc interacts with multiple protein partners to regulate synaptic transmission and nuclear signaling. The identification of calnexin as a binding partner further supports the role of Arc as a hub protein and extends the range of Arc function to the endoplasmic reticulum, though the function of the Arc/calnexin interaction remains to be defined. |
| first_indexed | 2024-12-13T04:48:04Z |
| format | Article |
| id | doaj.art-2eac5dd847c4436da3d15e8ae6604ecb |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-13T04:48:04Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-2eac5dd847c4436da3d15e8ae6604ecb2022-12-21T23:59:05ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-09-011110.3389/fncel.2017.00294294313Arc Interacts with the Integral Endoplasmic Reticulum Protein, CalnexinCraig Myrum0Craig Myrum1Jonathan Soulé2Margarethe Bittins3Kyle Cavagnini4Kevin Goff5Silje K. Ziemek6Maria S. Eriksen7Sudarshan Patil8Adrian Szum9Rajeevkumar R. Nair10Clive R. Bramham11Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University HospitalBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayDepartment of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, NorwayActivity-regulated cytoskeleton-associated protein, Arc, is a major regulator of long-term synaptic plasticity and memory formation. Here we reveal a novel interaction partner of Arc, a resident endoplasmic reticulum transmembrane protein, calnexin. We show an interaction between recombinantly-expressed GST-tagged Arc and endogenous calnexin in HEK293, SH-SY5Y neuroblastoma and PC12 cells. The interaction was dependent on the central linker region of the Arc protein that is also required for endocytosis of AMPA-type glutamate receptors. High-resolution proximity-ligation assays (PLAs) demonstrate molecular proximity of endogenous Arc with the cytosolic C-terminus, but not the lumenal N-terminus of calnexin. In hippocampal neuronal cultures treated with brain-derived neurotrophic factor (BDNF), Arc interacted with calnexin in the perinuclear cytoplasm and dendritic shaft. Arc also interacted with C-terminal calnexin in the adult rat dentate gyrus (DG). After induction of long-term potentiation (LTP) in the perforant path projection to the DG of adult anesthetized rats, enhanced interaction between Arc and calnexin was obtained in the dentate granule cell layer (GCL). Although Arc and calnexin are both implicated in the regulation of receptor endocytosis, no modulation of endocytosis was detected in transferrin uptake assays. Previous work showed that Arc interacts with multiple protein partners to regulate synaptic transmission and nuclear signaling. The identification of calnexin as a binding partner further supports the role of Arc as a hub protein and extends the range of Arc function to the endoplasmic reticulum, though the function of the Arc/calnexin interaction remains to be defined.http://journal.frontiersin.org/article/10.3389/fncel.2017.00294/fullarccalnexinendoplasmic reticulumproximity ligation assayendocytosissynaptic plasticity |
| spellingShingle | Craig Myrum Craig Myrum Jonathan Soulé Margarethe Bittins Kyle Cavagnini Kevin Goff Silje K. Ziemek Maria S. Eriksen Sudarshan Patil Adrian Szum Rajeevkumar R. Nair Clive R. Bramham Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin Frontiers in Cellular Neuroscience arc calnexin endoplasmic reticulum proximity ligation assay endocytosis synaptic plasticity |
| title | Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin |
| title_full | Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin |
| title_fullStr | Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin |
| title_full_unstemmed | Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin |
| title_short | Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin |
| title_sort | arc interacts with the integral endoplasmic reticulum protein calnexin |
| topic | arc calnexin endoplasmic reticulum proximity ligation assay endocytosis synaptic plasticity |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00294/full |
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