Figure 5. Model of KChIP3 function.

Post biogenesis at the Golgi, mucin granules undergo maturation and are placed on path to fuse with the plasma membrane and release their contents. However, the mature granules recruit KChIP3 (unbound to Ca²⁺) and this event stalls their fusion to the plasma membrane. KChIP3 recruitment thus acts as a brake to control the number of granules that can fuse with the plasma membrane. Based on our findings we describe two situations: (A) In absence of intracellular Ca²⁺ oscillations, KChIP3 is bound to the granules preventing their secretion, and (B) Upon a rise in intracellular Ca²⁺ by RYR-induced Ca²⁺ oscillations, the KChIP3 on the granules binds Ca²⁺ and subsequently detaches thereby triggering their SNARE dependent fusion to the plasma membrane. The cells have therefore evolved a mechanism by imposing the recruitment of empty KChIP3 to mucin granules to stall their progression leading to fusion with plasma membrane. Abbreviations: Cyt.: cytosol, Ext.: extracellular medium.