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Regulation of Lipid Metabolism from the Nuclear Envelope
Shirin Bahmanyar1, 2, Sarah Barger 2, Shoken Lee2, Han Yang2
1Presenting and corresponding author, MCDB Department, Yale University, New Haven, CT, USA
2 MCDB Department, Yale University, New Haven, CT, USA
Lipid composition is a determinant of organelle identity. How the inner nuclear membrane (INM) domain of the ER establishes a unique lipid chemistry that contributes to its distinct identity is not known. Akin to the vesicular trafficking pathway, a unique bilayer lipid composition would confer INM identity by imparting distinct membrane properties and recruiting a subset of proteins with lipid binding domains. Metabolic changes in bilayer lipids of the INM could then accommodate nuclear envelope remodeling and promote NE-specific functions by controlling its membrane properties and protein composition. We use fluorescent live imaging and genome editing in both C. elegans embryos and vertebrate cells to understand how regulation of local lipid metabolism controls nuclear envelope identity and dynamics. We developed a fluorescent protein biosensor to detect and monitor metabolic changes of INM lipids in vertebrate cells. We showed that the INM lipid environment is unique and can contribute to sculpting the INM proteome via direct lipid-protein interactions that regulate protein stability. Here, we will discuss our most recent results in which we use the INM-specific fluorescent protein biosensor for the lipid diacylglycerol to monitor metabolic changes in INM lipids upon NE formation in open mitosis. Through these studies we discovered that lipid identity of the NE is established as ER-derived membranes wrap around segregated chromosomes after open mitosis. The unique lipid composition of the reforming NE driven by lipid metabolism cooperates with membrane-chromatin interactions to form a single, sealed nuclear compartment. 3D-EM tomography revealed that disruption of these processes results in ER-NE stacks at junctions where membranes invade the nucleus. We suggest that lipid identity acts as a gatekeeper to enable ER to NE conversion, which is essential for NE formation and dynamics.
Speakers
Shirin Bahmanyar