Turnover of Transmitter and Synaptic Vesicles at the Frog Neuromuscular Junction

Ceccarelli, B; Hurlbut, W P; Mauro, Alexander

doi:10.1083/jcb.57.2.499

Cited by 784 publications

(526 citation statements)

References 25 publications

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“…from a new stimulus may make them releasable. Alternatively, the replenishment of the RRP may be due to the re-deployment of the same vesicles that have recently undergone fusion (Aravanis et al 2003;Ceccarelli et al 1973;Pyle et al 2000). This can be represented either as the replenishment of the RRP from the RP, or as part of the 'open system' contribution, or both.…”

Section: Discussionmentioning

confidence: 99%

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Bui

Glavinović

2012

Cogn Neurodyn

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Short-term synaptic depression mainly reflects the depletion of the readily releasable pool (RRP) of quanta. Its dynamics, and especially the replenishment rate of the RRP, are still not well characterized in spite of decades of investigation. Main reason is that the vesicular storage and release system is treated as time-independent. If it is time-dependent all parameters thus estimated become problematic. Indeed the reports about how prolonged stimulation affects the dynamics are contradictory. To study this, we used patterned stimulation on the Schaeffer collateral fiber pathway and model-fitting of the excitatory post-synaptic currents (EPSC) recorded from CA1 neurons in rat hippocampal slices. The parameters of a vesicular storage and release model with two pools were estimated by minimizing the squared difference between the ESPC amplitudes and simulated model output. This yields the 'basic' parameters (release coupling, replenishment coupling and RRP size) that underlie the 'derived' and commonly used parameters (fractional release and replenishment rate). The fractional release increases when [Ca ?? ] o is raised, whereas the replenishment rate is [Ca ?? ] o independent. Fractional release rises because release coupling increases, and the RRP becomes less able to contain quanta. During prolonged stimulation, the fractional release remains generally unaltered, whereas the replenishment rate decreases down to *10 % of its initial value with a decay time of *15 s, and this decrease in the replenishment rate significantly contributes to synaptic depression. In conclusion, the fractional release is [Ca ?? ] odependent and stimulation-independent, whereas the replenishment rate is [Ca ?? ] o -independent and stimulation-dependent.

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Section: Discussionmentioning

confidence: 99%

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Bui

Glavinović

2012

Cogn Neurodyn

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“…On the other hand, the uptake of relatively high molecular mass markers into dense core secretory vesicles has been reported both in insulin-secreting [104] and chromaffin cell-derived PC12 cells [105], suggesting that the fusion pore must subsequently close, recapturing extracellular material. As in the nerve terminal [106], it now seems likely that such transient events are predominant at physiological levels of stimulation, where the rate of exocytosis does not exceed the cell's capacity for endocytosis [107]. Indeed, when the fate of the insulin-containing vesicle is imaged simultaneously in living beta cells, using either the low-molecular-mass dye acridine orange [82] or the vesicle cargo protein neuropeptide Y (NPY) fused to monomeric red fluorescent protein (mRFP) or The closed circle represents insulin, and v-(black) and t-(grey) N-ethyl-maleimide-sensitive fusion protein attachment receptors are shown initially tethering the vesicle and plasma membranes before catalysing the fusion of the two.…”

Section: Mechanisms Of Vesicle Release At the Cell Surface: Full Fusimentioning

confidence: 99%

Visualising insulin secretion. The Minkowski Lecture 2004

Rutter

2004

Diabetologia

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Insulin secretion from pancreatic islet beta cells is a tightly regulated process, under the close control of blood glucose concentrations, neural inputs and circulating hormones. Defects in glucose-triggered insulin secretion, possibly exacerbated by a decrease in beta cell mass, are ultimately responsible for the development of type 2 diabetes. A full understanding of the mechanisms by which glucose and other nutrients trigger insulin secretion will probably be essential to allow for the development of new therapies of type 2 diabetes and for the derivation of "artificial" beta cells from embryonic stem cells as a treatment for type 1 diabetes. I focus here on recent developments in our understanding of beta cell glucose sensing, achieved in part through the development of recombinant targeted probes (luciferase, green fluorescent protein) that allow islet beta cell metabolism and Ca 2+ handling to be imaged in situ in the intact islet with single cell resolution. Combined with classical biochemistry, these techniques show that the beta cell is uniquely poised, thanks to the expression of low levels of lactate dehydrogenase and plasma membrane lactate/monocarboxylate transporters, to channel glucose carbons towards oxidative metabolism, ATP synthesis and inhibition of AMP-activated protein kinase, a newly defined regulator of insulin release. I also discuss the molecular basis of the recruitment of secretory vesicles to the cell surface, analysed by the use of new imaging techniques including total internal reflection of fluorescence, as well as the "nanomechanics" of the exocytotic event itself.

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“…In a number of systems, a population of small vesicles has been found to appear in the apical cytoplasm concomitant with the removal of the redundant plasma membrane originating with granule fusion (1,3,11,15,25,26,27,32,35,37). These vesicles have been often interpreted as membrane patches that have been retrieved directly from the lumen and are in transit to other cell organelles, such as the Golgi complex or multivesicular bodies (1,3,25,27,35,37).…”

Section: De Camnli Et Al Stimulation Of Parotid Acinar Cellsmentioning

confidence: 99%

Dynamic changes of the luminal plasmalemma in stimulated parotid acinar cells. A freeze-fracture study.

Camilli¹,

Peluchetti²,

Meldolesi³

1976

The Journal of Cell Biology

112

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In the acinar cells of the rat parotid gland the two membranes participating in exocytosis, i.e., the luminal plasmalemma and the secretory granule membrane, are clearly distinguishable in freeze-fracture because of their different densities in particles. In order to obtain point-specific information about the fusion-fission of these two membranes that occurs during the secretory cycle, glands were studied at various times (5 min to 6 h) after stimulation with isoproterenol. We observed that, in the course of the release of secretion products and shortly afterwards, the enlarged luminal plasmalemma exhibits a mosaic organization consisting of an alternation of membrane patches of high (original plasmalemma) and low (fused granule membrane) particle density. The transition between these two patterns is usually sharp. Later, concomitant with the reformation of acinar canaliculi, the low particle density membrane is found at the cell surface but only bounding vacuolar infoldings, and then it finally disappears.These results suggest that (a) fusion of these membranes does not result in a random intermixing of the molecular components of the participating membranes, which retain their structural identity; and (b) the enlarged luminal plasmalemma reverts to its original size by a progressive, specific removal of the regions of low particle density from the cell surface.In secretory cells the exportable proteins are known to be vectorially transported from the site of synthesis to the extracellular space through a pathway which includes a number of distinct membrane-bounded organelles (8,9,23,24): in sequence, the rough endoplasmic reticulum, the Golgi complex, and the secretion granules. The content of the latter is then discharged by exocytosis, i.e., by fusion of the granule limiting membrane with the plasmalemma followed by an opening at the point of fusion (36). Since the transport of the secretion products between adjacent cell compartments occurs in bulk, by means of membrane-bounded vesicles, a concomitant transfer of membranes must be postulated.The fate of the transferred membrane is still debated. Biochemical studies carried out on various secretory systems have clearly shown that the turnover rate of the molecular components of all the membranes involved is much slower than that of the secretory products (28,29,46,47); thus, it is most likely that these molecular components are reutilized in several secretory cycles (28,29). However, the mechanisms of this reutilization are still unclear, since it is not known whether membrane patches, after fusing with a membrane of a

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Turnover of Transmitter and Synaptic Vesicles at the Frog Neuromuscular Junction

Cited by 784 publications

References 25 publications

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Visualising insulin secretion. The Minkowski Lecture 2004

Dynamic changes of the luminal plasmalemma in stimulated parotid acinar cells. A freeze-fracture study.

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