Please join the Randall Centre for Cell & Molecular Biophysics for their annual lecture:
Role of the endosomal network in cell and tissue organization
Speaker: Professor Marino Zerial, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Host: Professor Mathias Gautel
Endosomes are important organelles for the transport and sorting of endocytosed cargo but also for other functions, such as signal transduction, regulation of metabolism and stress response. Rab GTPases are key regulatory components required for the biogenesis of endosomes as well as of other cellular organelles. In particular, Rab5 is necessary for the biogenesis of the entire endo-lysosomal pathway in vivo. It regulates the specificity and directionality of endosome fusion via the recruitment of tethering effectors that lead membranes to dock and fuse, for which SNAREs alone are insufficient. EEA1 is a tethering factor that bridges a Rab5-positive early endosome with another vesicle harbouring Rab5. Upon binding, Rab5 induces an allosteric conformational change on EEA1, from extended to flexible, generating an entropic collapse force that helps to pull the membranes together.
This means that the Rab machinery regulates both organelle recognition and mechanics leading to membrane fusion. Complementary to this approach, we have been studying the structural organization of the Rab5 machinery on early endosomes, using correlative super-resolution and electron microscopy (SuperCLEM). The combination of in vitro and in vivo systems allows us to answer questions regarding the formation, dynamics and role of Rab domains in the context of endosome biogenesis, structure and function. We are now applying this knowledge and developing quantitative imaging and functional genomics approaches to explore the endocytic mechanisms underlying liver tissue organization and regeneration.