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bioRxiv · 10.1101/2024.01.27.577545

ACKR3 Proximity Labeling Identifies Novel G protein- and β-arrestin-independent GPCR Interacting Proteins

Hicks, C.·Gardner, J.·Eiger, D. S.·Camarda, N.·Pham, U.·Dhar, S.·Rodriguez, H.·Chundi, A.·Rajagopal, S.
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Abstract

The canonical paradigm of GPCR signaling recognizes G proteins and {beta}-arrestins as the two primary transducers that promote GPCR signaling. Recent evidence suggests the atypical chemokine receptor 3 (ACKR3) does not couple to G proteins, and {beta}-arrestins are dispensable for some of its functions. Here, we employed proximity labeling to identify proteins that interact with ACKR3 in cells devoid of {beta}-arrestin. We identified proteins involved in the endocytic machinery and evaluated a subset of proteins conserved across several GPCR-based proximity labeling experiments. We discovered that the bone morphogenic protein 2-inducible kinase (BMP2K) interacts with many different GPCRs with varying dependency on {beta}-arrestin. Together, our work highlights the existence of modulators that can act independently of G proteins and {beta}-arrestins to regulate GPCR signaling and provides important evidence for other targets that may regulate GPCR signaling. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/577545v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@56a61org.highwire.dtl.DTLVardef@18b17baorg.highwire.dtl.DTLVardef@c2bd55org.highwire.dtl.DTLVardef@11c39b0_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Hicks, C., Gardner, J., Eiger, D. S., Camarda, N., Pham, U., Dhar, S., Rodriguez, H., Chundi, A., Rajagopal, S.. 2024-01-28. ACKR3 Proximity Labeling Identifies Novel G protein- and β-arrestin-independent GPCR Interacting Proteins. https://doi.org/10.1101/2024.01.27.577545

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