Comparative Interactome Analysis of α-arrestin Families in Human and Drosophila

• DOI: 10.7554/elife.88328.2
• Publication Date: 2023-11-01T17:42:45Z
• Authors: Kyung-Tae Lee; Inez K.A. Pranoto; Soon-Young Kim; Hee-Joo Choi; Ngoc Bao To; Hansong Chae; Jeong-Yeon Lee; Jung-Eun Kim; Young V. Kwon; Jin-Wu Nam
• Keywords: Interactome; Arrestin

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