In Part 2 of his talk, DeBose-Boyd introduces a rare genetic disorder known as Schnyder Corneal Dystrophy (SCD). SCD is characterized by accumulation of cholesterol in the corneas of affected individuals, indicating that the genetic defect in SCD may affect cholesterol synthesis. Mutations in the UBIAD1 gene cause SCD – therefore, DeBose-Boyd’s lab sought to understand the role of UBIAD1 in regulation of cholesterol metabolism. They found that UBIAD1 acts as a sensor for levels of the metabolite GGpp, which enhances sterol-mediated ERAD of HMG CoA reductase. In the presence of GGpp, UBIAD1 releases HMG CoA reductase, leading to its proteasomal degradation. DeBose-Boyd’s lab also discovered a fascinating spatial regulation of UBIAD1, whereby binding of UBIAD1 to GGpp causes UBIAD1 to accumulate in the Golgi apparatus and away from HMG CoA reductase in the ER. Finally, his group found that the SCD-associated mutation N102S in UBIAD1 inhibits the interaction between UBIAD1 and GGpp, such that mutant UBIAD1 is unable to translocate from the ER to the Golgi in the presence of high GGpp.
View the full talk with additional resources on our website
Regulation of Cholesterol Synthesis
Dr. Russell DeBose-Boyd describes cellular regulation of cholesterol synthesis, with a focus on endoplasmic reticulum-associated degradation (ERAD) of HMG CoA reductase. (Talk recorded in August 2019)
- Part 1: Feedback Regulation of HMG CoA ReductaseAudience:
- Student
- Researcher
- Educators of H. School / Intro Undergrad
- Educators of Adv. Undergrad / Grad
Duration: 00:23:47 - Part 2: Schnyder Corneal Dystrophy: Importance of UBIAD1 in Regulation of CholesterolAudience:
- Student
- Researcher
- Educators of Adv. Undergrad / Grad
Duration: 00:16:35