Comparative interactome analysis of α-arrestin families in human and Drosophila .
Kyung-Tae LeeInez K A PranotoSoon-Young KimHee-Joo ChoiNgoc Bao ToHansong ChaeJeong-Yeon LeeJung-Eun KimYoung V KwonJin-Wu NamPublished in: eLife (2024)
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.
Keyphrases
- endothelial cells
- transcription factor
- induced pluripotent stem cells
- mass spectrometry
- pluripotent stem cells
- signaling pathway
- dna methylation
- dna damage
- gene expression
- high throughput
- postmenopausal women
- ms ms
- hiv infected
- bone loss
- men who have sex with men
- soft tissue
- induced apoptosis
- high throughput sequencing
- recombinant human