Structure modeling hints at a granular organization of the Vertebrate Golgi ribbon

Vertebrate cells display a specific Golgi apparatus architecture, known as the "ribbon", where the functional subunits, the mini-stacks, are linked into a tridimensional network. The importance of the ribbon architecture is underscored by evidence of its disruption in a host of diseases, but just how it relates to the biological Golgi functions remains unclear. Are all the connections between mini-stacks functionally equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, due to the lack of a secretory cargo providing a quantifiable readout of the functional output of ribbon-embedded mini-stacks. Endothelial cells produce rod-shaped secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. In these cells, the Golgi apparatus exerts a dual control on WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF boluses" while the ribbon architecture allows their linear co-packaging at the trans-Golgi network generating WPBs of different lengths. This Golgi/WPB size relationship lends itself to mathematical analysis. Here, different ribbon structures were modeled and their predicted effects on WPB size distribution compared to the ground truth of experimental data. Strikingly, the best-fitting model describes a Golgi ribbon made by linked subunits corresponding to differentially functioning monomer and dimer ministacks. These results raise the intriguing possibility that the fine-grained structure of the Golgi ribbon is more complex than previously thought.