The nuclear envelope (NE) represents the hallmark of eukaryotic cells and evolved as an essential protective membrane system as well as a key platform for nuclear signaling, genome organization, cargo transport, mechanosensation, and etc. Despite of its importance, the NE composition has been poorly understood in eukaryotic species beyond humans and yeasts. In this talk, I will share our recent progresses in defining the protein landscape of nuclear membrane in plants and in-depth functional investigation of newly identified NE proteins. In addition, I will talk about how the nucleocytoplasmic transport receptors, proteins that carry macromolecules to cross the NE, function as a critical plant immune regulator via modulating biomolecular condensation and protein phase separation of their cargo, representing an ancient function that predates the evolution of eukaryotes.
Eph receptors make up the largest subfamily of receptor tyrosine kinases in mammals. These receptors are responsible for communication between adjacent cells during development and in adult tissue homeostasis. Dysregulation of Eph receptors is widely implicated in a variety of diseases. Humans express a total of 14 Eph receptors, divided into A and B subfamilies, and 8 types of ephrin ligands. Activation of Eph receptors appears to involve either homotypic or heterotypic self-association. For some Eph receptors, homo-dimerization is postulated to be sufficient for the activation of the kinase domain, but others appear to function by either hetero-dimerization or higher-order oligomerization. Here, we focus on the molecular mechanism of EphA3, an Eph receptor whose dysregulation promotes motility of breast cancer cells. By purifying EphA3 fused with an optogenetic tag that permits the reversible assembly of homo-and hetero-oligomers, we will be able to carefully determine the number of Eph receptors needed to form a minimal functional cluster and explore how the different protomers in the cluster work together to elicit kinase activity.
2:15-2:45 Endocytosis-Driven Polarity and Migration in Breast Cancer Cells
Emily Chan,
Kural lab
Breast cancer is the most diagnosed cancer worldwide and a leading cause of death in women, largely due to metastasis. Key mechanisms in metastasis involve cell migration, which depends on (1) establishing adhesion to the extracellular matrix (ECM) through focal adhesions (FAs) and clathrin-containing adhesion complexes (CCACs) and (2) endocytosis for internalizing extracellular molecules. FAs and CCACs anchor cells to the ECM, while endocytosis dynamically regulates adhesion sites to enable migration. Dysregulated endocytosis in cancer enhances cell detachment and invasion, making it essential to understand how it contributes to cell polarity during migration. My research investigates how nonuniform endocytic activity drives asymmetric FA and CCAC distributions. Using advanced microscopy and engineered microscale environments, I analyze these dynamics in migrating breast cancer cells. Our results indicate that inhibiting endocytosis at the cell rear significantly reduces migration, while inhibition at the front enhances migration. Additionally, endocytic asymmetry appears to influence FA and CCAC distribution, underscoring endocytosis’s role in cellular polarity. Our research has the potential to identify new therapeutic targets that could disrupt metastasis by interfering with endocytosis-mediated migration.
Last update: 11/5/2024, Ralf Bundschuh