Youngah Jo, Jason S Hamilton, Seonghwan Hwang, Kristina Garland, Gennipher A Smith, Shan Su, Iris Fuentes, Sudha Neelam, Bonne M Thompson, Jeffrey G McDonald, Russell A DeBose-Boyd
Autosomal-dominant Schnyder corneal dystrophy (SCD) is characterized by corneal opacification owing to overaccumulation of cholesterol. SCD is caused by mutations in UBIAD1, which utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2 . Using cultured cells, we previously showed that sterols trigger binding of UBIAD1 to the cholesterol biosynthetic enzyme HMG CoA reductase (HMGCR), thereby inhibiting its endoplasmic reticulum (ER)-associated degradation (ERAD) (Schumacher et al. 2015). GGpp triggers release of UBIAD1 from HMGCR, allowing maximal ERAD and ER-to-Golgi transport of UBIAD1...
February 20, 2019: ELife