Modeling Rab-dependent intracellular transport. SAIB 10-13 noviembre, Tucumán. Biocell

MAYORGA, L.S.; CAMPOY, E

Tucumán

Congreso; SAIB XLV; 2009

SAIB

A fundamental feature of eukaryotic cells is the presence of distinct membrane-bound compartments having unique protein and lipid composition.  These compartments 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. It is well accepted that Rabs play a central role in intracellular transport regulating the recognition, fusion and fission of organelles.  However, how the transport is achieved is not completely understood.  Our aim was to propose a model where a soluble component in the luminal compartment is transported along different Rab-containing organelles that interact according to the following simple hypothetical principles: i) only organelles with the same or compatible Rab domains can fuse, ii) after fusion, an asymmetric fission occurs rendering a tubule and a round-shaped vesicle, and iii) Rab domains distribute asymmetrically in the two resulting organelles. When this model was tested in a simulation, an efficient and unidirectional transport was observed; and at the same time, the compartment identity was preserved. All three principles were absolutely necessary for transport.  The model is compatible with Rab dynamics and it predicts that a misbalance in Rab composition, either for an excess or a defect, affects cargo transport