Molecular mechanism of the formation of transport intermediates in the post-golgi retrograde transport route

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Project objective

Early endosomes are sorting stations communicating with the plasma membrane ( endocytosis and recycling) and with late endosomes / lysosomes (classical endocytic pathway) . It has been observed the existence of yet an alternative route, from the early endosome directly to the trans-Golgi network, possibly implicating the recycling endosome. Endogenous proteins, such as TGN38, and the B-subunit of Shiga toxin have been shown to follow this route. Its physiological role has not yet been elucidated, but recent evidence has been provided that it is used by signaling molecules such as interferon alpha/beta receptors and CD14 to reach internal sites from where there may signal to their targets. This project aims at the reconstitution of the formation of intermediates of retrograde transport, either from early/recycling endosomes , or in a reconstituted liposomal system. The role of different proteins (SNAREs, coat proteins, cargo) and their functional interactions with membrane microsomains ( rafts " ) will be studied. Our work will reveal the molecular mechanism of protein and lipid targeting into the retrograde transport route and shed light on how lateral lipid asymmetry in biological membranes may influence this process. In addition, it may also lead to the discovery of new therapeutic targets involved in the intracellular transport of signaling receptors and help to optimize the use o f Shiga toxin B subunit as a vector for the intracellular delivery of therapeutics compounds."

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Participants

• INSTITUT CURIE · PARISCoordinatorFrance

Links

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