Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin
Craig Myrum1,2, Jonathan Soulé2, Margarethe Bittins2
1Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University HospitalBergen, Norway.
Frontiers in Cellular Neuroscience
|October 6, 2017
Summary
Researchers discovered that Activity-regulated cytoskeleton-associated protein (Arc) interacts with calnexin, an endoplasmic reticulum protein. This novel interaction, crucial for synaptic plasticity and memory, occurs in neurons and is enhanced during long-term potentiation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Activity-regulated cytoskeleton-associated protein (Arc) is critical for synaptic plasticity and memory.
- Arc regulates AMPA-type glutamate receptors and synaptic transmission.
- Calnexin is a resident endoplasmic reticulum transmembrane protein involved in protein folding and quality control.
Purpose of the Study:
- To identify novel interaction partners of Arc.
- To investigate the functional significance of Arc and calnexin interaction.
- To explore the role of this interaction in neuronal plasticity.
Main Methods:
- Recombinant protein expression and co-immunoprecipitation in various cell lines (HEK293, SH-SY5Y, PC12).
- High-resolution proximity-ligation assays (PLAs) in cultured hippocampal neurons and adult rat dentate gyrus.
- In vivo electrophysiology to induce long-term potentiation (LTP) in anesthetized rats.
- Transferrin uptake assays to assess receptor endocytosis.
Main Results:
- A novel interaction between Arc and calnexin was identified and validated across multiple cell types.
- The interaction is mediated by the central linker region of Arc.
- Arc specifically interacts with the cytosolic C-terminus of calnexin in neurons.
- Enhanced Arc-calnexin interaction was observed in the dentate gyrus following LTP induction.
- No modulation of transferrin uptake was detected, suggesting the interaction does not directly impact general receptor endocytosis.
Conclusions:
- Calnexin is a novel binding partner of Arc, extending Arc's functional repertoire to the endoplasmic reticulum.
- The Arc-calnexin interaction is dynamically regulated during synaptic plasticity.
- Arc functions as a molecular hub, integrating synaptic activity with intracellular processes.
- The precise functional role of the Arc-calnexin interaction warrants further investigation.
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