Function suggests nano-structure: electrophysiology supports that granule membranes play dice

Abstract

Cellular communication depends on membrane fusion mechanisms. SNARE proteins play a fundamental role in all intracellular fusion reactions associated with the life cycle of secretory vesicles, such as vesicle -vesicle and vesicle plasma membrane fusion at the porosome base in the cell plasma membrane. We present growth and elimination (G&E), a birth and death model for the investigation of granule growth, its evoked and spontaneous secretion and their information content. Using a statistical mechanics approach in which SNARE components are viewed as interacting particles, the G&E model provides a simple 'nanomachine' of SNARE self-aggregation behind granule growth and secretion. Results from experimental work, mathematical calculations and statistical modelling suggest that for vesicle growth a minimal aggregation of three SNAREs is required, while for the evoked secretion one SNARE is enough. Furthermore, the required number of SNARE aggregates (which varies between cell types and is nearly proportional to the square root of the mean granule diameter) affects and is statistically identifiable from the size distributions of spontaneous and evoked secreted granules. The new statistical mechanics approach to granule fusion is bound to have a significant changing effect on the investigation of the pathophysiology of secretory mechanisms and methodologies for the investigation of secretion.

Function suggests nano-structure: towards a unified theory for secretion rate, a statistical mechanics approach

“…The authors have developed a growth and elimination (G&E) model that describes a possible mechanism for basal granule growth and secretion [5,16]. According to this model, homogeneous unit granules are packaged in the Golgi apparatus (or otherwise), with some mean content (i.e.…”

“…Exocytic events of release-ready vesicle pool from secretory cells [1 -3] follow a time course consistent with calcium concentration [4] and with Poisson behaviour [5,6], as evidenced by a number of statistical measures, such as the estimate of its rate, the number of events recorded per unit time [6]. For vesicular secretion, this direct measure exhibits a variety of statistical properties that can be monitored.…”

“…between cellular Ca 2þ signals and catalysed by specific proteins (mainly SNAREs) [1][2][3][4][5][6][7][8][9][10][11]. The delivery of newly formed secretory content to the cytoplasm granule inventory occurs through a direct fusion of recently formed granules and mature granules.…”

“…For vesicular secretion, this direct measure exhibits a variety of statistical properties that can be monitored. In particular, the probability of granule fusion with the plasma membrane, which establishes the rate of secretion, is highly dependent on random SNARE protein aggregation in a rosette at the porosome base [5], arrival time and biochemical activity [1][2][3][4][5][6]. Based on statistical mechanics modelling composed with meta-analysis of experimental data, we propose a generalization of the common formula [4] …”

The Secretory Portal- Porosome in Pancreatic Acinar Cells

“…Therefore, these structures were named 'porosomes' (36,43,46) or secretory portals in cells. Our own studies and studies from other laboratories established porosomes to be secretory portals that perform the specialized task of fractional discharge of intravesicular contents from cells during secretion (20,23,26,32,36,43,46,49,52,54,56,61). The significance of the identification of the porosome is reflected by several publications regarding the structure and the associated transient fusion mechanism by fractional discharge of intravesicular contents from cells (3,20,23,26,32,49,52,54,56,61,68,69).…”