Modeling fusion/fission-dependent intracellular transport of fluid phase markers.

LUIS MAYORGA; EMANUEL CAMPOY

TRAFFIC

WILEY-BLACKWELL PUBLISHING, INC

Lugar: La Jolla; Año: 2010 vol. 11 p. 1001 - 1015

1398-9219

A fundamental feature of eukaryotic cells is the presenceof distinct membrane-bound compartments havingunique protein and lipid composition. These compartmentsare interconnected by active trafficking mechanismsthat must direct macromolecules to defined locations,and at the same time maintain the protein and lipidcomposition of each organelle. It is well accepted that Rabproteins play a central role in intracellular transport regulatingthe recognition, fusion and fission of organelles.However, how the transport is achieved is not completelyunderstood. We propose a modelwhereby a soluble componentin the luminal compartment is transported alongdifferent Rab-containing organelles that interact accordingto the following simple principles: (i) only organelleswith the same or compatible Rab membrane domainscan fuse; (ii) after fusion, an asymmetric fission occursproducing a tubule and a round-shaped vesicle; and(iii) Rab membrane domains distribute asymmetricallybetween the two resulting organelles. When this modelwas tested in a simulation, efficient unidirectional transportwas observed, while the compartment identity waspreserved. All three principles were absolutely necessaryfor transport. The model is compatible with Rab association/dissociation dynamics and with Rab conversion.In simulations mimicking a simplified endocytic pathway,soluble and membrane-associated markers wereefficiently transported preserving the identity of the interactingcompartments.