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SUMMARY:Role of the endosomal network in cell and tissue organization - Pr
 ofessor Marino Zerial from Max Planck Institute of Molecular Cell Biology 
 and Genetics\, Dresden 
DTSTART:20190425T130000Z
DTEND:20190425T140000Z
UID:TALK109288@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Endosomes are important organelles for the transport and sorti
 ng of endocytosed cargo but also for other functions\, such as signal tran
 sduction\, regulation of metabolism and stress response. Rab GTPases are k
 ey 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 SNARE
 s alone are insufficient. EEA1 is a tethering factor that bridges a Rab5-p
 ositive 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 pulling th
 e membranes together. This means that the Rab machinery regulates both org
 anelle recognition and mechanics leading to membrane fusion. Complementary
  to this approach\, we have been studying the structural organization of t
 he Rab5 machinery on early endosomes\, using correlative super-resolution 
 and electron microscopy (SuperCLEM). The combination of in vitro and in vi
 vo systems allows us to answer questions regarding the formation\, dynamic
 s and role of Rab domains in the context of endosome biogenesis\, structur
 e and function. We are now applying this knowledge and developing quantita
 tive imaging and functional genomics approaches to explore the endocytic m
 echanisms underlying liver tissue organization and regeneration.
LOCATION:Biffen Lecture Theatre\, Department of Genetics\, Downing Site
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