Regulated exocytosis is known as the operational mechanism by which specific organelles, secretion granules/vesicles, fuse their membrane with the plasmalemma in response to an appropriate signal and thus release their content to the extracellular space. Other forms of exocytosis exist, concerning for example vesicles generated at the trans-Golgi network and recycling endosomes. In the latter case, however, membrane fusion is not regulated but constitutive. The two processes are therefore believed to be substantially different, both in terms of mechanisms and physiological significance. Based on this (by the way, almost generally accepted) view, regulated exocytosis is the process responsible for quantal secretion and exists therefore in specialized secretory cells (neurons, endocrine, exocrine, etc.) while the other cells are competent only for constitutive exocytosis.

A few years ago, capacitance studies carried out first in fibroblasts, (i.e. non-secretory cells CHO and 3T3) then in a defective clone of the pheochomocytoma line, PC12, that our previous work had shown to be completely incompetent for regulated neurosecretion, demonstrated that [Ca²⁺]_i increases induced by photolysis of caged Ca²⁺ are able to induce a rapid increase of the cell surface, apparently similar to the response triggered by the same treatment in cells competent for neurosecretion. Detailed analysis of this response demonstrated it to be sustained by the fusion of small vesicles (< 100 nm in diameter) and to occur by a membrane fusion type independent of the classical SNAREs, syntaxin 1, VAMP 2 and SNAP 25. Working in the defective PC12 clone as well as in a variety of other cell types we have now identified the new endocytotic system. The specific organelle is a vesicle recognized by the expression of a protein we have named Marker of Exocytotic Vesicles (MarEx). This marker is localized within the vesicle and appears at the surface only by Ca²⁺-triggered exocytosis. MarEx is expressed by many, although not all types of cells. In some of them, for example in wild-type PC12 treated with NGF, expression occurs only during differentiation. Moreover, MarEx appears at the surface of cells which had been wounded, suggesting its participation in wound healing.

We conclude that another form of exocytosis exists in addition to the classical secretory form. In nerve cells the latter is specific for clear vesicles and dense granules. The new form is in contrast specific for another type of vesicle which might have nothing to do with secretion but be responsible for rapid enlargements of the plasma membrane. In view of this possibility we suggest the vesicles competent for this form of exocytosis to be called enlargesomes.