Profile
Project Title: Regulation of E-cadherin-mediated cell-cell adhesion by the microtubule cytoskeleton
Summary:
E-cadherin, a transmembrane protein localised to the lateral surfaces of polarised epithelial cells, is a fundamental component of adherens junctions and is crucial for maintaining epithelial homeostasis. Dysregulation of E-cadherin is a well-established contributor to pathogenesis across multiple organ systems and is a hallmark of the epithelial-to-mesenchymal transition (EMT), a process that enhances the invasiveness and metastatic potential of carcinomas.
Emerging evidence, including preliminary data from our laboratory, indicates that the microtubule is critically involved in regulating the correct localisation and stability of E-cadherin. Microtubules function as polarised filaments that serve as primary tracks for intracellular transport. While the mechanisms regulating E-cadherin delivery to adhesion sites remain incompletely characterised, our findings suggest the involvement of the motor protein dynein. Furthermore, multi-protein complexes assembled at dynamic MT plus ends, via plus-end tracking proteins, recruit and modulate signalling components such as RhoA GTPase regulators with the potential to modulate E-cadherin adhesions.
My project aims to systematically dissect the molecular mechanisms and functional consequences of E-cadherin regulation by microtubules. I will employ a multidisciplinary strategy, combining genetic, live-cell imaging, and biochemical assays. This research is anticipated to provide fundamental insights into the control of epithelial integrity.
Supervisor: Dr Natalia Bulgakova