Fig. 8. Cell surface presentation and secretion of epimorphin and its extracellular action for epithelial morphogenesis. Intracellular epimorphin becomes complexed with synaptotagmin (syt) and annexin II, both of which can directly bind to phosphatidylserine at the inner leaflet of the plasma membrane. In response to stress and/or Ca²⁺ influx, this release complex translocates across the membrane with externalization of phosphatidylserine. The extracellularly presented epimorphin is then cleaved at the SNARE domain and the secreted form of epimorphin is captured by v-integrin on the target epithelia leading to FAK activation and initiation of morphogenesis. The role of cytoplasmic epimorphin as a t-SNARE protein in SNARE-mediated membrane fusion (inset). EX, extracellular space. IN, intracellular space. Syb, synaptobrevin, Epm, epimorphin.