Kiss-and-run, full or partial exocytosis? The next question is how to degranulate
As MCs reach their destination and encounter a secretagogue, the secretory actin phenotype overrides the migratory actin phenotype, relieving the secretory constraints 80. MCs then enter a state in which they can undergo exocytosis. This can take place in three different ways: i) individual SGs move to the plasma membrane where they dock and fuse with the membrane and release their full content; ii) by compound exocytosis where SGs fuse with each other, forming a channel through which they release their content; or iii) “kiss-and-run exocytosis” where SGs only transiently fuse with the membrane and release only part of their content 81. Choosing the mode of exocytosis bears physiological significance, as the distinct features and dynamics of the different exocytic modes are associated with unique physiological responses 82(Figure 3). At the molecular level, two factors have been identified as critical for defining the degranulation pattern. The first is the enzyme IKKβ, whose activity is required for the phosphorylation of the SNARE protein SNAP23, which is essential for SG fusion during compound exocytosis 81-83. The second is the small GTPase Rab5, which plays a role in SG fusion during both their biogenesis84 and compound exocytosis 85.
In conclusion, the underlying mechanisms that regulate MCs during their life cycle are only beginning to be clarified. They include mechanisms that ensure MC homing to destined tissues, recruitment to inflammatory areas, prevention of premature secretion and selection of the mode of exocytosis. Future studies will shed light on these mechanisms and the molecular entities involved.