Degranulation relies on transport by an induced microtubule network (green, right).

Degranulation of mast cells involves a two-step process, report Nishida et al. on page 115. First, antigen stimulation triggers microtubule polymerization and granule translocation to the cell surface in a calcium-independent process. Second, the granules fuse with the plasma membrane in a well-characterized calcium-dependent process.

Mast cells are so full of granules that degranulation was thought to occur through granule-to-membrane fusion and granule-to-granule fusion, without the need for granule transport. However, inhibition of microtubule polymerization blocked degranulation.

In response to antigen stimulation, Nishida et al. found that tubulin staining increased and fluorescently tagged granules translocated to the cell surface before exocytosis. Removal of calcium from the culture medium prevented granule fusion to the membrane but had no effect on microtubule polymerization or granule movement, suggesting that the steps are distinct.

When the team stimulated mast cells deficient for Fyn or Lyn tyrosine kinase signaling proteins, the cells had reduced degranulation, as previously reported. However, only the Fyn mutant cells showed a disruption in microtubule polymerization and granule movement, suggesting that Fyn signaling directs microtubule polymerization.The scientists are now looking for proteins that link granules to microtubules. They reason that such molecules might provide a relatively specific target for drugs aimed at blocking unwanted histamine release from mast cells.