Characterization of the role of the small GTPase Rab7b in intracellular traffic.

Intracellular trafficking is regulated by Rab proteins. More than 60 human Rabs have been identified but until now there has been no Rab assigned to the transport from TGN to late endosomes/lysosomes. In our recent work (Progida et al, under revision), we show that Rab7b is a strong candidate for this pathway. Rab7b is highly expressed in blood cells, including dendritic cells (DCs). DCs present antigens via their MHC class II (MHC II) molecules. MHC II is assembled in the ER and transported to endosomal compartments for antigen loading. The exact route and machinery involved in this transport has not been definitively established. Several reports suggest that the complex is transported directly from the trans-Golgi network (TGN) to endosomes and Invarian t chain (Ii) plays an important role in this pathway. Therefore in this project we will test if Rab7b has a role in the trafficking of Ii and MHC II to loading compartments. In order to answer this question we will use live imaging in DCs depleted of or o verexpressing Rab7b. The Bakke`s lab is running the Oslo NorMIC imaging node and they have developed a system for studying trafficking events in intracellular pathway towards the immune specific compartment for peptide loading. An understanding of these p rinciples may have wide ranging applications in basic cell biology, immune therapy, vaccination and a general understanding of cellular immune functions.