MODELING RAB-DEPENDENT INTRACELLULAR TRANSPORT

MAYORGA, LUIS; CAMPOY, EMANUEL MARTIN

Tucuman

Congreso; Reunion SAIB XLV; 2009

A fundamental feature of eukaryotic cells is the presence of distinctmembrane-bound compartments having unique protein and lipidcomposition. These compartments are interconnected by activetrafficking mechanisms that must direct macromolecules to definedlocations, and at the same time maintain the protein and lipidcomposition of each organelle. It is well accepted that Rabs play acentral role in intracellular transport regulating the recognition,fusion and fission of organelles. However, how the transport isachieved is not completely understood. Our aim was to propose amodel where a soluble component in the luminal compartment istransported along different Rab-containing organelles that interactaccording to the following simple hypothetical principles: i) onlyorganelles with the same or compatible Rab domains can fuse, ii)after fusion, an asymmetric fission occurs rendering a tubule and around-shaped vesicle, and iii) Rab domains distributeasymmetrically in the two resulting organelles. When this modelwas tested in a simulation, an efficient and unidirectional transportwas observed; and at the same time, the compartment identity waspreserved. All three principles were absolutely necessary fortransport. The model is compatible with Rab dynamics and itpredicts that a misbalance in Rab composition, either for an excessor a defect, affects cargo transport.