Figure 7.

Final model including endocytosis and back-translation to interaction graph. The developed model with ATP/endocytosis included and back-translation to an interaction graph, including the cell physiological insights from this work. In agreement with the original model (Fig. 1A), adiponectin exocytosis is triggered by cAMP alone and augmented by the combination of ATP and Ca²⁺. As revealed by this study, ATP is also required in combination with Ca²⁺ in order for adiponectin-containing vesicles to attain release competence (in our model, to be transferred from the reserve pool to the releasable pool). In addition to stimulating exocytosis, Ca²⁺ also induces membrane retrieval (endocytosis). The Ca²⁺-triggered endocytosis needs to be preceded by cAMP-triggered exocytosis (cf. Fig. 3C). The contribution of Ca²⁺-dependent endocytosis to the measured signal is substantial at unphysiologically high intracellular Ca²⁺ concentrations (see text for more details).