PMID- 28979192 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 11 DP - 2017 TI - Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin. PG - 294 LID - 10.3389/fncel.2017.00294 [doi] LID - 294 AB - 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. FAU - Myrum, Craig AU - Myrum C AD - Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University HospitalBergen, Norway. AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Soule, Jonathan AU - Soule J AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Bittins, Margarethe AU - Bittins M AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Cavagnini, Kyle AU - Cavagnini K AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Goff, Kevin AU - Goff K AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Ziemek, Silje K AU - Ziemek SK AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Eriksen, Maria S AU - Eriksen MS AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Patil, Sudarshan AU - Patil S AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Szum, Adrian AU - Szum A AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Nair, Rajeevkumar R AU - Nair RR AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. FAU - Bramham, Clive R AU - Bramham CR AD - Department of Biomedicine and the K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of BergenBergen, Norway. LA - eng PT - Journal Article DEP - 20170920 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC5611444 OTO - NOTNLM OT - arc OT - calnexin OT - endocytosis OT - endoplasmic reticulum OT - proximity ligation assay OT - synaptic plasticity EDAT- 2017/10/06 06:00 MHDA- 2017/10/06 06:01 PMCR- 2017/01/01 CRDT- 2017/10/06 06:00 PHST- 2017/07/12 00:00 [received] PHST- 2017/09/05 00:00 [accepted] PHST- 2017/10/06 06:00 [entrez] PHST- 2017/10/06 06:00 [pubmed] PHST- 2017/10/06 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2017.00294 [doi] PST - epublish SO - Front Cell Neurosci. 2017 Sep 20;11:294. doi: 10.3389/fncel.2017.00294. eCollection 2017.