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.