Comparative interactome analysis of α-arrestin families in human and Drosophila

Author:

Lee Kyung-Tae12ORCID,Pranoto Inez KA3ORCID,Kim Soon-Young4ORCID,Choi Hee-Joo567ORCID,To Ngoc Bao1,Chae Hansong1,Lee Jeong-Yeon56ORCID,Kim Jung-Eun4,Kwon Young V3ORCID,Nam Jin-Wu125ORCID

Affiliation:

1. Department of Life Science, College of Natural Sciences, Hanyang University

2. Hanyang Institute of Advanced BioConvergence, Hanyang University

3. Department of Biochemistry, University of Washington

4. Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University

5. Bio-BigData Center, Hanyang Institute for Bioscience and Biotechnology, Hanyang University

6. Department of Pathology, College of Medicine, Hanyang University

7. Hanyang Biomedical Research Institute, Hanyang University

Abstract

The α-arrestins form a large family of evolutionally conserved modulators that control diverse signaling pathways, including both G-protein-coupled receptor (GPCR)-mediated and non-GPCR-mediated pathways, across eukaryotes. However, unlike β-arrestins, only a few α-arrestin targets and functions have been characterized. Here, using affinity purification and mass spectrometry, we constructed interactomes for 6 human and 12 Drosophila α-arrestins. The resulting high-confidence interactomes comprised 307 and 467 prey proteins in human and Drosophila, respectively. A comparative analysis of these interactomes predicted not only conserved binding partners, such as motor proteins, proteases, ubiquitin ligases, RNA splicing factors, and GTPase-activating proteins, but also those specific to mammals, such as histone modifiers and the subunits of V-type ATPase. Given the manifestation of the interaction between the human α-arrestin, TXNIP, and the histone-modifying enzymes, including HDAC2, we undertook a global analysis of transcription signals and chromatin structures that were affected by TXNIP knockdown. We found that TXNIP activated targets by blocking HDAC2 recruitment to targets, a result that was validated by chromatin immunoprecipitation assays. Additionally, the interactome for an uncharacterized human α-arrestin ARRDC5 uncovered multiple components in the V-type ATPase, which plays a key role in bone resorption by osteoclasts. Our study presents conserved and species-specific protein–protein interaction maps for α-arrestins, which provide a valuable resource for interrogating their cellular functions for both basic and clinical research.

Funder

National Research Foundation of Korea

Korea Basic Science Institute

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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