Investigation of the function of ORP2 sterol binding in neurotransmitter release and membrane contact sites

• Applicant: Marion Weber-Boyvat, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 525595786

The aim of the proposal is to unravel the sterol sensing mechanism of the lipid transfer protein ORP2 in murine hippocampal neurons. The focus is set on the characterization the cell biological consequences of ORP2s sterol dependent interactions with the plasma membrane SNAREs Stx1A and SNAP-25 as well as the ER-protein VAPA. This will be achieved by a combination of electrophysiological, biochemical and microscopical methods. A special focus will be given to cholesterol level modulation to integrate ORP2s input in the context of disease linked to high and low cholesterol. In addition to sterol sensing, ORP2s interplay with the essential active zone scaffold Munc13-1 will be exploded, using specific interaction deficient mutants and advanced fluorescent inducible oligomerization-tags. The long-term goal of this project is to realize how ORP2, in cooperation with its interacting proteins, can translated specific membrane cholesterol compositions to specific cell biological processes.

• DFG Programme: Research Grants
• International Connection: Finland
• Cooperation Partners: Professor Vesa Olkkonen; Dr. Hongxia Zhao