Modeling fusion/fission-dependent intracellular transport.

MAYORGA LS; CAMPOY, E

Puerto Madryn

Congreso; SAIB; 2010

MODELING FUSION/FISSION-DEPENDENT INTRACELLULAR TRANSPORT Mayorga LS, Campoy, E IHEM (UNCuyo-CONICET), Fac. Cs. Médicas, UNCuyo, Mendoza. E-mail: lmayorga@fcm.uncu.edu.ar Eukaryotic cells have distinct membrane-bound compartments that are interconnected by active trafficking mechanisms that must direct macromolecules to defined locations, and at the same time maintain the protein and lipid composition of each organelle.  Hundred of factors have been implicated in intracellular transport by overexpression and knockout experiments; however, how they control and mediate transport is not well understood. By modeling iterative events of organelle fusion and fission we demonstrated that luminal components are efficiently transported when geometric asymmetries between the resulting organelles were programmed. In contrast, transport of membrane-associated components was inefficient.  We have extended our model to assess the requirement for membranous marker transport during iterative fusion/fission events in simulations that include recycling and formation of internal vesicles.  The results indicate that two basic principles are required:  i) only organelles with the same or compatible Rab membrane microdomains (MMD) can fuse, ii) during fission, Rab MMD and the membrane marker distribute asymmetrically in the two resulting organelles.  With these rules, membrane markers were directed to “lyososomal” compartments or “recycled” to the extracellular medium according to the tropism assigned to the marker during the fission processes.