Paulsen lab publishes article on the functional consequences of a human TRPA1 variant linked to chronic pain

May 22, 2023

A drastic TRPA1 mutation was identified in patients with CRAMPT syndrome in 2018, but how it could contribute to their pronounced pain phenotype has confused the field for years. In a team effort led by Paulsen Lab graduate student Avnika Bali, postgraduate researcher Samantha Schaefer, and undergraduate student and MBB peer mentor Alice Zhang (pictured) in collaboration with MBB colleagues Isabelle Trier and Lily Kabeche, they have solved this conundrum by uncovering the unexpected molecular mechanism by which this mutant confers gain-of-function. Mutant subunits co-assemble with WT TRPA1 subunits to form hyperactive heteromeric channels. These results expand the physiological impact of nonsense mutations, uncover insights into the process of TRPA1 gating, and provide an impetus for genetic analysis of patients with CRAMPT or other stochastic pain syndromes. These results have been published in Nature Communications.