Fig. 7

Modeling lysosomal transport from TGN to endosomes. A RabE domain (yellow, shown as a TGN compartment in Fig. 1a) containing a lysosomal enzyme (HexA-like cargo) bound to a membrane-associated transporter (M6PR-like cargo) were included in the simulation. RabE organelles interact with RabB endosomes. The M6PR was given affinity to RabE domains. The reversible dissociation of HexA from M6PR was programmed as a pH-regulated reaction in COPASI (Tables 1, 2, and 3). a Histogram of pH for RabE structures from 3 simulations (30 min runs). b The amount of soluble HexA (dissociated from M6PR) present in RabD and RabE structures was recorded along the simulation. After dissociation at low pH, HexA behaved as a soluble cargo and accumulated in RabD structures. c Same as in b, showing the association of the HexA with RabA, RabB, and RabC endosomes or recycled to the plasma membrane. Notice the very low values even for the expanded scale used. d The amount of M6PR present in RabB and RabE structures was recorded along the simulation. Most of the receptor was retained in RabE structures. e Enlarged scale to show that a small percentage of M6PR was found in RabB and RabC endosomes. The levels were low in RabA and RabD structures. Part of M6PR was transported to the plasma membrane. Data on panel b to e correspond to the average of 8–10 independent simulations