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Affinity proteomics identifies novel functional modules related to adhesion GPCRs.

Barbara Knapp1, Jens Roedig1, Karsten Boldt2

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|August 24, 2019
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Summary

Adhesion G protein-coupled receptors (ADGRs) play roles in cell signaling and adhesion. New research reveals their involvement in intracellular membranes and gene regulation, expanding our understanding of ADGR protein networks.

Keywords:
ADGRG protein-coupled receptorsWnt signalingaGPCRgamma-secretasemitochondria-associated membranessynaptic scaffold proteins

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Proteomics

Background:

  • Adhesion G protein-coupled receptors (ADGRs) possess a unique structure combining G protein-coupled receptor signaling with adhesive extracellular domains.
  • While ADGR signaling is increasingly understood, their protein interaction networks remain largely uncharacterized.
  • Identifying ADGR interaction partners is crucial for elucidating their cellular functions.

Purpose of the Study:

  • To identify novel interaction partners of ADGRs.
  • To investigate the cellular protein networks involving ADGRs.
  • To explore the functional roles of ADGRs beyond cell surface interactions.

Main Methods:

  • Affinity proteomics utilizing tandem affinity purification.
  • Mass spectrometry for comprehensive analysis of protein interactions.
  • Bioinformatic analysis of proteomics data.

Main Results:

  • ADGRs are implicated in functions at synapses and intracellular membranes, including the endoplasmic reticulum, Golgi apparatus, mitochondria, and mitochondria-associated membranes (MAMs).
  • Identified associations include membrane-associated guanylate kinase scaffold proteins, γ-secretase complex components, mitochondrial proteins, MAM proteins, and Wnt signaling regulators.
  • Nuclear localization of ADGR domains and interactions with nuclear proteins and transcription factors suggest a role in gene regulation.

Conclusions:

  • ADGRs participate in diverse cellular processes beyond adhesion and synaptic function.
  • The study expands the known interactome of ADGRs, revealing novel roles in intracellular membrane trafficking and gene regulation.
  • These findings provide a foundation for further research into the multifaceted roles of ADGRs in cellular networks.