Porocytosis: Secretion from small and medium-diameter vesicles and vesicle arrays without membrane fusion

Abstract

We have recently proposed a mechanism to describe secretion, a fundament 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 (Silver et al., 2001; Kriebel et al., 2001). Energetics of apposed lipid bilayers do not favor unfacilitated fusion. Calcium ion levels are elevated in microdomains at levels of 10(-4)-10(-3)M for 1 ms or less, with the calcium ions showing limited lateral mobility at the site of secretion (Llinas et al., 1992, Silver et al., 1994). We consider that calcium ions, whose mobility is restricted in space and time, establish "salt-bridges" among adjacent lipid molecules, and establishes transient pores that span the vesicle and plasma membrane lipid bilayers; the lifetime of that transient pore being completely dependent on duration of sufficient calcium ion levels.

Kiss‐and‐run and full‐collapse fusion as modes of exo‐endocytosis in neurosecretion

“…Additional labels include ‘transient fusion’ (Elhamdani et al . 2006), ‘fuse‐pinch‐and‐linger’ (Ryan 2003), ‘porocytosis’ (Silver et al . 2003).…”

SNARE proteins as molecular masters of interneuronal communication

“…Molecular studies have revealed that synaptotagmin I is predominantly associated with the complete synaptic vesicle fusion, while synaptotagmin IV predominantly leads to "kiss-and-run" exocytosis (29). The latter secretion from small and medium-diameter vesicles and vesicle arrays without complete membrane fusion, is also known as "porocytosis" (30). A detailed review of the porosome structure and dynamics as revealed by atomic force microscopy is given by Jena in this volume (31).…”

Porocytosis: A transient pore array secretes the neurotransmitter packet

“…In the mechanism we propose, presynaptic vesicles are anchored to the active zone of the plasma membrane and juxtaposed to calcium ion‐selective channels by proteins such as SNARE (Sudhof, 2000). Calcium ions resulting from the action potential bind with the lipid bilayers of vesicles and plasmalemma to form an array of transient pores to release some transmitter from each docked vesicle (Silver et al, 2003). The array pulses a standard packet of transmitter, which in turn generates the postsynaptic quantal response.…”

“…By comparison, the nerve terminal is only 1 micron in diameter and therefore activation of the secretory apparatus would be expected to occur within a millisecond. The extent of the calcium microdomain is the synaptomere (Silver et al, 1994; Sugimori et al, 1994; Kriebel and Keller, 1999; Silver et al, 2003). In the presynaptic neuromuscular junction, the synaptomere extends 1 micron across the terminal diameter and is 200 nanometers wide.…”