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Talk by Dominik Oliver

Title: "A metabolic PI(4,5)P2 microdomain maintains lipid transport function at ER-PM junctions"
Occasion: SFB - Seminar
Start: 30.11.2023 - 16:15
Location: CellNanOs, 38/201

About the speaker: Prof. Dr. Simon Newstead conducts research about Neurophysiology at the Institut for Physiology and Pathophysiology, University of Marburg.

Abstract of the talk: In the last few years, endoplasmic reticulum-plasma membrane contact sites (‘ER-PM junctions') have been recognized as the central hubs of lipid flux between both membrane compartments. This process is key to PLC and PI3 kinase signaling as it involves transport of phosphatidylinositol (PtdIns) from ER to PM, which is required for the homeostatic PI(4,5)P2 synthesis that fuels both pathways. PtdIns transfer is needed most when PI(4,5)P2 levels in the PM drop. Paradoxically, current understanding indicates that the PtdIns transfer relies on the presence of PI(4,5)P2 in the PM, because tether proteins that connect both membranes rely on PI(4,5)P2 to anchor the lipid transport platform to the PM. To address this puzzle, we used tubbyCT, a coincidence sensor of PI(4,5)P2 and E-Syt3 to examine PI(4,5)P2 dynamics at E-Syt3-rich ER-PM junctions. Under conditions of vigorous PI(4,5)P2 consumption by PLCβ, recruitment of tubbyCT revealed an increase of a junctional PI(4,5)P2 pool fed by local synthesis through PI kinases. Inhibition of this pool-filling process led to the release of the ER-PM tethers from the PM and attenuation of lipid transfer activity. We conclude that spatiotemporal metabolic channeling of PI synthesis at ER-PM junctions specifies a local pool of PI(4,5)P2 that is pivotal for the maintenance of homeostatic function during global depletion of PI(4,5)P2.