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Signal transduction in receptor for advanced glycation end products (RAGE): solution structure of C-terminal rage

Vivek Rai1, Andres Y Maldonado, David S Burz

  • 1New York University Medical Center, New York, New York 10016, USA.

The Journal of Biological Chemistry
|December 24, 2011
PubMed

Insights

The receptor for advanced glycation end products (RAGE) cytoplasmic domain binds mDia1 via an α-turn, crucial for RAGE signaling in inflammation and neurodegeneration.

Area of Science:

  • Cellular biology
  • Molecular mechanisms
  • Signal transduction

Background:

  • Receptor for advanced glycation end products (RAGE) is implicated in diabetes complications, inflammation, and neurodegeneration.
  • The cytoplasmic domain of RAGE (ctRAGE) is essential for RAGE-mediated signal transduction.
  • mDia1 interaction with ctRAGE is critical for RAGE ligand-stimulated AKT phosphorylation and cell proliferation/migration.

Purpose of the Study:

  • To elucidate the structural basis of the mDia1-ctRAGE interaction.
  • To determine the role of this interaction in RAGE-dependent signaling pathways.

Main Methods:

  • Structural analysis of ctRAGE
  • Biochemical assays to study protein interactions
  • Cellular assays to assess RAGE signaling

Main Results:

  • Identified an unusual α-turn within ctRAGE.
  • Demonstrated that this α-turn mediates the interaction between mDia1 and ctRAGE.
  • Confirmed the necessity of the mDia1-ctRAGE interaction for RAGE signaling.

Conclusions:

  • A novel mechanism for RAGE signaling involving an α-turn in ctRAGE and mDia1 interaction is established.
  • This finding provides new insights into the regulation of RAGE-dependent cellular responses.

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