Secretion without membrane fusion: Porocytosis

Abstract

We have recently proposed a mechanism to describe secretion, a fundamental process in all cells. That hypothesis, called porocytosis, embodies all available data and encompasses both forms of secretion, i.e., vesicular and constitutive. The current accepted view of exocytotic secretion involves the physical fusion of vesicle and plasma membranes; however, that hypothesized mechanism does not fit all available physiological data. Energetics of apposed lipid bilayers do not favor unfacilitated fusion. We consider that calcium ions (e.g., 10(-4) to 10(-3) M calcium in microdomains when elevated for 1 ms or less), whose mobility is restricted in space and time, establish salt bridges among adjacent lipid molecules. This establishes transient pores that span both the vesicle and plasma membrane lipid bilayers; the diameter of this transient pore would be approximately 1 nm (the diameter of a single lipid molecule). The lifetime of the transient pore is completely dependent on the duration of sufficient calcium ion levels. This places the porocytosis hypothesis for secretion squarely in the realm of the physical and physical chemical interactions of calcium and phospholipids and places mass action as the driving force for release of secretory material. The porocytosis hypothesis that we propose satisfies all of the observations and provides a framework to integrate our combined knowledge of vesicular and constitutive secretion.

Dense-core granules in neuroendocrine cells and neurons release their secretory constituents by piecemeal degranulation (Review)

“…Recently, an alternative (or complementary) mode of exocytosis has been proposed as a means of DCG release. This process has been variably referred to as 'kissand-run' exocytosis, 'fuse-pinch-and-linger', 'cavicapture' or 'porocytosis' (22)(23)(24)(25)(26). Accordingly, the granule limiting membrane contacts the plasma membrane and a transient and reversible fusion pore is established.…”

Mast Cell Mediators: Their Differential Release and the Secretory Pathways Involved

“…This review identifies our current understanding of the biogenesis of various mediator compartments, and the mechanisms of sorting and release of mediators from these compartments (Figure 1 ). We present some new postulates about exocytosis that may be particularly relevant to the MC, a highly specialized secretory cell ( 13 ). We also refer the readers some excellent recent articles for more details on various aspects of this subject ( 9 , 14 – 19 ).…”

Using enrichment index for quality control of secretory protein sample and identification of secretory proteins

“…Calcium ion could establish salt bridges among adjacent lipid molecules on plasma membrane. Some intracellular components were allowed to go out of the cells through these transient pores 29. In another study, the Tat protein of HIV which mainly promotes replication of HIV in the nucleus could also be secreted into the extracellular space and became part of the extracellular matrix 30.…”