Membrane contact sites are cellular regions where two organelles come into proximity, facilitated by specific proteins that not only create a physical connection but also serve distinct functions like lipid transport, calcium signaling, or organelle inheritance. They exhibit diversity in their shapes, compositions, and dynamics, with intermembrane gaps spanning from 10 to 45 nm across distances up to several hundreds of nanometers. We are interested in the transport of cholesterol between ER and Golgi apparatus mediated by the tethering proteins, VAP-A and OSBP. We used cryo-electron tomography and advanced imaged analysis to get different 3D molecular architectures of in vitro reconstituted membrane contact sites. This also revealed the molecular requirement for the assembly-disassembly of protein complexes within a confined space between apposed organelles.

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