Figure 1.

Main stages of biogenesis and secretory pathways of mast cell carboxypeptidase A3 (adapted from Atiakshin [84]). The diagram shows the main stages of post-translational modification of CPA3 with an emphasis on cytotopography, intragranular localization, and secretory mechanisms. CPA3 biosynthesis begins in the granular endoplasmic reticulum mast cells (MC) and continues in the Golgi apparatus (GA), where the progranule is formed. Secretory granules (SG) can be classified into 3 types. Type I SGs are formed after fusion of lysosomes with progranules, budding from GA, and have the smallest size and initial CPA3 content. The size of type I granules can increase due to homotypic fusion with the formation of type II granules with a size of 0.2–0.4 μm. Type II secretory granules already possess a certain phenotype of specific proteases. As a result of the completion of maturation, type III SGs are formed with a size of 0.5 μm and more, which are characterized by the largest volume of secretome and peripheral localization of CPA3 in the form of a ring. The main mechanisms of CPA3 secretion from MC into the extracellular matrix are piecemeal degranulation, transgranulation, «kiss-and-run», exosome formation, exocytosis of individual secretory granules, as well as the formation of macrovesicles that retain the ability for autonomous secretion of proteases in a specific tissue microenvironment.