A disease-causing G protein switch

Abstract

Developmental Disorders Mutations in components of the endothelin signaling pathway prevent the nervous system from developing properly, which results in the craniofacial defects characteristic of auriculocondylar syndrome (ACS). Some ACS patients have mutations in Gαi3, a G protein subunit that is not normally part of the endothelin signaling pathway. Marivin et al. found that the Gαi3 mutations associated with ACS enabled Gαi3 to bind inappropriately to an endothelin receptor and block the binding of another G protein. Because the Gαi3 mutants lacked enzymatic activity, they prevented the receptor from signaling. Sci. Signal. 9 , ra37 (2016).