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Published on: July 30, 2014
Arc/Arg3.1 has an activity-regulated interaction with PICK1 that results in altered spatial dynamics
Brandee M S S Goo1, Bethany J Sanstrum1, Diana Z Y Holden1
1Department of Cell and Molecular Biology, John A. Burns School of Medicine, 651 Ilalo St., BSB 222, University of Hawaii, Honolulu, HI, 96813, USA.
Activity-regulated cytoskeleton-associated protein (Arc) directly interacts with protein interacting with C-terminal kinase 1 (PICK1). This novel interaction, enhanced by depolarization, suggests PICK1 mediates Arc
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Activity-regulated cytoskeleton-associated protein (Arc) regulates AMPAR endocytosis during LTD.
- Protein interacting with C-terminal kinase 1 (PICK1) is involved in AMPAR trafficking.
Purpose of the Study:
- To investigate the interaction between Arc and PICK1.
- To elucidate the role of PICK1 in Arc-mediated AMPAR regulation.
Main Methods:
- Co-immunoprecipitation using Arc as bait.
- Fluorescence lifetime imaging microscopy (FLIM) and Förster resonance energy transfer (FRET) analysis.
- Live-cell imaging and analysis of protein puncta.
Main Results:
- Arc directly interacts with PICK1.
- The interaction is enhanced under depolarizing conditions.
- Arc binding occurs within the first 126 amino acids of the PICK1 BAR domain.
- PICK1 mediates Arc regulation of AMPARs, especially during depolarization.
Conclusions:
- A novel interaction between Arc and PICK1 is identified.
- PICK1 plays a crucial role in mediating Arc's function in AMPAR regulation.
- This interaction is particularly relevant under conditions of neuronal depolarization.
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