Redefining Hypo- and Hyper-Responding Phenotypes of CFTR Mutants for Understanding and Therapy.

ABSTRACT: Mutations in CFTR cause misfolding and decreased or absent ion-channel function, resulting in the disease Cystic Fibrosis. Fortunately, a triple-modulator combination therapy (Trikafta) has been FDA-approved for 178 mutations, including all patients who have F508del on one allele. That so many CFTR mutants respond well to modulators developed for a single mutation is due to the nature of the folding process of this multidomain protein. We have addressed the question 'What characterizes the exceptions: the mutants that functionally respond either not or extremely well'. A functional response is the product of the number of CFTR molecules on the cell surface, open probability, and conductivity of the CFTR chloride channel. By combining biosynthetic radiolabeling with protease-susceptibility

SUBMITTER: Hillenaar T 

PROVIDER: S-EPMC9735543 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature