Interplay between ALK2^R206H mutant receptor and autophagy signaling regulates receptor stability and its chondrogenic functions.

ABSTRACT: Heterozygous mutations in the Bone morphogenetic protein (BMP) type I receptor ACVR1, encoding activin-like kinase 2 (ALK2), underlie all cases of the rare genetic musculoskeletal disorder Fibrodysplasia Ossificans Progressiva (FOP). The most commonly found mutant ALK2 p.R206H receptor variant exhibits loss of auto inhibition of BMP signaling and can be activated by Activins, while wild-type receptors remain unresponsive. Consequently, the downstream chondrogenic signaling is enhanced, thus driving heterotopic ossification within soft connective tissues. Despite several investigational treatments being evaluated in clinical trials, no cure for FOP exists today. The cellular and molecular mechanisms underlying disease progression are still being deciphered. In this study, we show a close in

SUBMITTER: Coculo L 

PROVIDER: S-EPMC11929866 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature