Porosome: the Universal Secretory Machinery in Cells

Secretion and membrane fusion are fundamental cellular processes regulating endoplasmic reticulum (ER)–Golgi transport, plasma membrane recycling, cell division, sexual reproduction, acid secretion, and the release of enzymes, hormones, and neurotransmitters, to name just a few. It is therefore no surprise that defects in secretion and membrane fusion give rise to diseases such as diabetes, Alzheimer’s, Parkinson’s, acute gastroduodenal diseases, gastroesophageal reflux disease, intestinal infections due to inhibition of gastric acid secretion, biliary diseases resulting from malfunction of secretion from hepatocytes, polycystic ovarian disease as a result of altered gonadotropin secretion, and Gitelman disease associated with growth hormone deficiency and disturbances in vasopressin secretion. Understanding cellular secretion and membrane fusion not only helps to advance our understanding of these vital cellular and physiological processes, but also helps in the development of drugs to ameliorate secretory defects, provides insight into our understanding of cellular entry and exit of viruses and other pathogens, and helps in the development of smart drug delivery systems. Therefore, secretion and membrane fusion play an important role in health and disease. Studies (Abu-Hamdah et al., 2004; Anderson, 2004; Cho et al., 2002a–f, 2004; Hörber and Miles, 2003; Jena, 1997, 2002–2004; Jena et al., 1997, 2003; Jeremic et al., 2003, 2004a,b; Kelly et al., 2004; Schneider et al., 1997) in the last decade demonstrate that membrane-bound secretory vesicles dock and transiently fuse at the base of specialized plasma membrane structures called porosomes or fusion pores, to expel vesicular contents. These studies further demonstrate that during secretion, secretory vesicles swell, enabling the expulsion of intravesicular contents through porosomes (Abu-Hamdah et al., 2004; Cho et al., 2002f; Jena et al., 1997; Kelly et al., 2004). With these findings (Abu-Hamdah et al., 2004; Anderson, 2004; Cho et al., 2002a–f, 2004; Hörber and Miles, 2003; Jena, 1997, 2002–2004; Jena et al., 1997, 2003; Jeremic et al., 2003, 2004a,b; Kelly et al., 2004; Schneider et al., 1997) a new understanding of cell secretion has emerged and confirmed by a number of laboratories (Aravanis et al., 2003; Fix et al., 2004; Lee et al., 2004; Taraska et al., 2003; Thorn et al., 2004; Tojima et al., 2000).