Characterization of a caveolin-1 mutation associated with both PAH and congenital generalized lipodystrophy
Bing Han, Courtney A. Copeland, Yumeko Kawano, Erika Berman Rosenzweig, Eric D. Austin, Layla Shahmirzadi, Sha Tang, Krishnan Raghunathan, Wendy K. Chung and Anne K. Kenworthy
Accepted manuscript online: 26 SEP 2016 09:10AM EST | DOI: 10.1111/tra.12452
We identify a heterozygous F160X mutation in the caveolin-1 (CAV1) gene in a patient with both pulmonary arterial hypertension (PAH) and congenital generalized lipodystrophy (CGL) and examine its effect on caveolae assembly. We find that the mutant protein forms hybrid caveolae together with wild type CAV1 in patient skin fibroblasts and reconstituted CAV1−/− MEFs but that these caveolae are abnormal in several respects. These caveolaer defects may serve as contributing factors to the development of PAH and CGL.