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

Abstract

The inventory of secretory granules along the plasma membrane can be viewed as maintained in two restricted compartments. The release-ready pool represents docked granules available for an initial stage of fast, immediate secretion, followed by a second stage of granule set-aside secretion pool, with significantly slower rate. Transmission electron microscopy ultrastructural investigations correlated with electrophysiological techniques and mathematical modelling have allowed the categorization of these secretory vesicle compartments, in which vesicles can be in various states of secretory competence. Using the above-mentioned approaches, the kinetics of single vesicle exocytosis can be worked out. The ultra-fast kinetics, explored in this study, represents the immediately available release-ready pool, in which granules bound to the plasma membrane are exocytosed upon Ca .

‘Porosome’ discovered nearly 20 years ago provides molecular insights into the kiss‐and‐run mechanism of cell secretion

“…), and further established using high‐resolution EM . This SNARE rosette arrangement between opposing bilayers during membrane fusion is now widely accepted and published as the fundamental structure of the t‐/v‐SNARE complex associated with membrane fusion and cell secretion .…”

Neuronal porosome – The secretory portal at the nerve terminal: Its structure–function, composition, and reconstitution

“…In contrast a slow secretory cell like the exocrine pancreas, possess larger secretory vesicles measuring >1000 nm in diameter, that transiently fuse at porosomes that have bases measuring nearly 20 nm in diameter. Therefore within the small volume that the fusion reaction is known to take place, it is suggested (Hammel and Meilijson, 2012, 2013) that classical biophysics may play a minor role and that the approach of statistical mechanics should be considered.…”

Quantal Basis of Secretory Granule Biogenesis and Inventory Maintenance: the Surreptitious Nano-machine Behind It

“…We documented in early stages of our work that granule size distribution shows a better fit to the unit addition mechanism 18,19 . Later work 8,9,11 established the necessity to move away from classical biochemical and biophysical approaches (that assumed all monomers to be initially present and restricted granule size distributions to the two families above) 20 in favor of a particle Physics approach under which a "packaging machine" produces unit granules of monomer size that coalesce with mature granules by the unit addition mechanism. The resulting SNARE-driven G&E model is the basis of our hypothesized modedependent stochastic polymer-size single-letter communication language.…”

“…Cells communicate with each other primarily through secretion. We have recently proposed 11,21 that basal (or constitutive, spontaneous) and evoked ( The first recorded evidence for slow secretion dealt with neurosecretory synapses. This type of secretion, coined minis (for miniature neurotransmission) and hypothesized as a transsynaptic process where single synaptic vesicles spontaneously secrete from pre-synaptic neurons and induce miniature postsynaptic potentials 23 , does not induce neurons to fire and was thus considered as insignificant background noise.…”

“…The values obtained for the rosette size pairs had K γ ranging between 4 and 9 and K β usually equal to but in some cases exceeding K γ by 1. Kvalues as high as 30 have been discussed in the literature [9][10][11] . Theoretical calculations show that the inequality K γ ≤ K β +1 is necessary and sufficient for the existence of a stationary solution to the G&E model.…”