Redefining the concept of protease-activated receptors: Cathepsin S evokes itch via activation of Mrgprs

Vemuri B. Reddy, Shuohao Sun, Ehsan Azimi, Sarina B. Elmariah, Xinzhong Dong, Ethan A. Lerner

Research output: Contribution to journalArticlepeer-review

Abstract

Sensory neurons expressing Mas-related G-protein-coupled receptors (Mrgprs) mediate histamine-independent itch. We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-dependent scratching in mice. In contrast to its activation of conventional protease-activated receptors, cathepsin S-mediated activation of MrgprC11 did not involve the generation of a tethered ligand. We demonstrate further that different cysteine proteases selectively activate specific mouse and human Mrgpr family members. This expansion of our understanding by which proteases interact with G-protein-coupled receptors (GPCRs) redefines the concept of what constitutes a protease-activated receptor. The findings also implicate proteases as ligands to members of this orphan receptor family while providing new insights into how cysteine proteases contribute to itch.

Original languageEnglish (US)
Article number7864
JournalNature communications
Volume6
DOIs
StatePublished - Jul 28 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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