Despite its less-than-stellar reputation in the news, cholesterol is an essential molecule for living things. It serves as the building block for hormones and helps give shape to the membranes that enclose cells and their internal parts. Consequently, many diseases arise from defects in the proper transport of cholesterol. Now, researchers at Osaka University have shed new light on one of the key pathways used to transport cholesterol inside of cells.
The researchers set out to demystify non-vesicular transport using a screening assay, which allowed them to find proteins that interact with known players in the pathway. From this screening, they identified RELCH. Although not previously connected to cholesterol transport, RELCH was found to interact with two critical proteins in the pathway: Rab11 and OSBP. These interactions laid the initial groundwork for the key discovery in the study.
“Non-vesicular transport is thought to happen when two membranes tether together, allowing cholesterol to jump from one membrane to the next,” Sobajima adds. “We set up an artificial system that lets us measure how well cholesterol moves along tethered cell membranes. What we found was that Rab11-containing membranes (or beads) and OSBP-containing membranes (or beads) tether together very effectively when RELCH is added to the mix, and cholesterol can then move easily across the membranes”