Mechanism of mast cell activation in patients with vibratory urticaria

Authors

• AN Naranjo
• HD Komarow
• SE Boyden
• A Desai
• MA Beaven
• DD Metcalfe
• A Olivera

Abstract

Upon dermal vibration, patients with vibratory urticaria (VU) experience localized hives and increased histamine levels in serum. These responses are caused by hyperreactivity of skin mast cells to a mechanical stimulus. We found that patients with a familial form of VU harbor a missense substitution in an adhesion G-protein coupled receptor (aGPCR), ADGRE2, that renders mast cells more susceptible to vibration-induced activation. However, the mechanisms of activation of ADGRE2 and how this mutation enhances the ability of mast cells to respond to a mechanical stimulus is not understood. In the present study, we detail the signaling pathways activated through the ADGRE2 receptor upon ligand binding and vibration. Our results provide insights into the structural requirements for ADGE2 activation, how it signals and possible therapeutic targets for patients with VU.

Scientific Focus Area: Molecular Biology and Biochemistry

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