Fig. 1

Model description. a Informal model for transport along the endocytic route. Different Rab domains characterize four organelles: early endosomes (RabA), sorting endosomes (RabB), recycling endosomes (RabC), and late endosomes (RabD). A trans-Golgi network (TGN) is included as a RabE organelle for modeling transport of lysosomal enzymes (Figs. 7, 8 and 9). The straight lines represent microtubules that orientate the organelle movements. The brown arrows represent the movement of cargoes to recycling endosomes and to late endosomes/lysosomes. b Fusion and asymmetric fission. A RabA (blue perimeter) endosome carrying a membrane-bound cargo (red internal circle) and a soluble cargo (green content) fuses with an empty RabB (cyan) endosome. The hybrid vesicle has enough membrane to embrace the volume of the original endosomes, to form an internal vesicle, and to grow a tubule. When the tubule is separated from the round organelle, it carried the RabB domain, the red cargo and an amount of soluble cargo proportional to its volume. At the bottom, the way these organelles are representation in the model. The red and green contents are shown in the interior of the RabA organelle (yellow content). The color of the endosomes corresponds to the prevailing Rab in each organelle. After fusion, the resulting organelle is shown as an ellipse representing the ellipsoid with a size, and area/volume ration of the fused organelle. The color is set to blue because it is the prevailing Rab domain in the organelle. The interior is set to light yellow, because of the dilution of the green and red contents, and a “1” character is plotted indicating that the organelle carries an internal vesicle. After fission, the round organelle is represented as a circle with a blue perimeter, a “1” character (the internal vesicle), and a light green internal color, showing that part of the soluble content and all the membrane cargo went to the tubule. The tubule is represented by an elongated ellipse, with a cyan color corresponding to the RabB domain, and an orange interior representing the red content and part of the green content. c Informal representation of the Rab dynamics operating in the model (cut-out switch, [22]). Each Rab domain stimulates its own activation. In addition, RabA promotes RabD activation and RabD inhibits RabA activation. This dynamic was programmed in COPASI and the species, reactions, kinetic functions, and parameters are shown in Table 3. d Diagram of the simulation. Initially, Repast builds a set of organelles specified by parameters and characteristics read from a file (Additional file 1). The program then initiates an iterative loop where each agent is interrogated about performing or not a series of actions and changing its properties accordingly. The simulation records the evolution of the system and receives instructions from the user by periodically writing and reading external files (Additional file 2)