Targeting PI3Kγ anchoring enhances CFTR membrane localization and modulator efficacy via PKD1 - PubMed
4 hours ago
- #Cystic Fibrosis
- #PI3Kγ
- #CFTR Modulators
- Mutations in the CFTR gene cause cystic fibrosis (CF), a common inherited disorder among White individuals.
- Current CFTR modulators like elexacaftor-tezacaftor-ivacaftor (ETI) only partially restore F508del-CFTR function, leaving residual disease.
- A PI3Kγ mimetic peptide (PI3Kγ MP) enhances F508del-CFTR membrane localization and maximizes ETI efficacy by elevating localized cAMP.
- PI3Kγ MP activates PKD1, which regulates membrane trafficking, and PKD1 inhibition prevents the peptide's effect on CFTR membrane expression.
- Targeting the AKAP function of PI3Kγ presents a new pathway to improve CFTR modulator therapies.