RELOCATION OF THE T-SNARE SNAP-23 FROM LAMELLIPODIA-LIKE CELL-SURFACEPROJECTIONS REGULATES COMPOUND EXOCYTOSIS IN MAST-CELLS

For regulated secretion, mast cells and several other cell types utili ze compound exocytosis, a combination of granule-plasma membrane and g ranule-granule fusions. The molecular machinery that controls this mas sive export process has not been identified. We report that SNAP-23, a t-SNARE related to SNAP-25, relocates in response to stimulation from plasma membrane lamellipodia-like projections to granule membranes in permeabilized mast cells. While relocation is a prerequisite for secr etion, it can occur without membrane fusion and will expedite a subseq uent secretory response. After relocation, SNAP-23 is required for exo cytosis, implying a crucial role in promoting membrane fusion. Thus, r elocation of this SNARE regulates compound exocytosis and links granul e-plasma membrane and granule-granule fusions.