Author response: The readily-releasable pool dynamically regulates multivesicular release

SUMMARY The distribution of neurosecretory granules in various anatomical compartments of neurosecretory axons of the neural lobe of the rat pituitary has been studied. Apart from the most anterior tip of the gland, where granules are largely restricted to undilated axons and a few 'swellings', the proportional compartmental storage of granules is essentially homogeneous for the rest of the gland: 13% of granules are found in undilated axons, 31% in axonal 'endings' (which contain microvesicles and abut the basement membrane) and 55% in axonal 'swellings' (which are devoid of significant numbers of microvesicles). These values indicate that the 'endings' contain a much greater proportion of the total number of granules stored in the neural lobe than would be predicted if the readily releasable pool of hormone were composed of all the granules in the 'endings'. Some further constraint on granule release either physiological or anatomical (e.g. the position of the granule in relation to the plasmalemma of the 'ending') must be operative.

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Is replenishment of the readily releasable pool associated with vesicular movement?

Cognitive Neurodynamics ◽

10.1007/s11571-013-9264-y ◽

2013 ◽

Vol 8 (2) ◽

pp. 99-110 ◽

Cited By ~ 3

Author(s):

Loc Bui ◽

Mladen I. Glavinović

Keyword(s):

Releasable Pool ◽

Readily Releasable Pool

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VARIATION IN SIZE OF THE 'READILY RELEASABLE POOL' OF LUTEINIZING HORMONE DURING THE OESTROUS CYCLE OF THE RAT

Journal of Endocrinology ◽

10.1677/joe.0.0830053 ◽

1979 ◽

Vol 83 (1) ◽

pp. 53-59 ◽

Cited By ~ 26

Author(s):

A. J.-M. C. PICKERING ◽

G. FINK

Keyword(s):

Luteinizing Hormone ◽

Fold Increase ◽

Pool Size ◽

Oestrous Cycle ◽

Apparent Increase ◽

Storage Pool ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Significant Change

SUMMARY The size of the 'readily releasable pool' of luteinizing hormone at various times of the oestrous cycle has been determined by injecting a supramaximal dose of luteinizing hormone releasing factor (LH-RF) i.v. into rats anaesthetized with sodium pentobarbitone. In an attempt to block replenishment of the 'pool' during release, cycloheximide was administered 30 min before LH-RF. A 20-fold increase in pool size occurred between the morning of dioestrus and the evening of pro-oestrus in the absence of any significant change in total pituitary content of LH. This suggests that increased responsiveness may be brought about by a change in the receptor-release apparatus and/or a transfer of LH from a 'storage pool' which leads to an apparent increase in the proportion of LH available for release.

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Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles

PLoS Biology ◽

10.1371/journal.pbio.1002267 ◽

2015 ◽

Vol 13 (10) ◽

pp. e1002267 ◽

Cited By ~ 44

Author(s):

Taulant Bacaj ◽

Dick Wu ◽

Jacqueline Burré ◽

Robert C. Malenka ◽

Xinran Liu ◽

...

Keyword(s):

Synaptic Vesicles ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Synaptotagmin 1

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A Simple Depletion Model of the Readily Releasable Pool of Synaptic Vesicles Cannot Account for Paired-Pulse Depression

Journal of Neurophysiology ◽

10.1152/jn.00554.2006 ◽

2007 ◽

Vol 97 (1) ◽

pp. 948-950 ◽

Cited By ~ 10

Author(s):

Jane M. Sullivan

Keyword(s):

Synaptic Vesicles ◽

Hippocampal Neurons ◽

Synaptic Activity ◽

Excitatory Synapses ◽

Short Term ◽

Paired Pulse ◽

Short Term Plasticity ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Paired Pulse Depression

Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses.

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A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

Scientific Reports ◽

10.1038/srep09517 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 8

Author(s):

Jun Guo ◽

Jian-long Ge ◽

Mei Hao ◽

Zhi-cheng Sun ◽

Xin-sheng Wu ◽

...

Keyword(s):

Time Course ◽

Current View ◽

Vesicle Recycling ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Central Synapse ◽

Pool Model ◽

Underlying Mechanisms ◽

First Time ◽

Intense Stimulation

Abstract Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP) and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles.

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Synaptotagmin 1 clamps synaptic vesicle fusion in mammalian neurons independent of complexin

Nature Communications ◽

10.1038/s41467-019-12015-w ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 13

Author(s):

Nicholas A. Courtney ◽

Huan Bao ◽

Joseph S. Briguglio ◽

Edwin R. Chapman

Keyword(s):

Synaptic Vesicle ◽

Vesicle Fusion ◽

Snare Proteins ◽

Major Focus ◽

C2 Domains ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Synaptotagmin 1 ◽

Synaptic Vesicle Fusion ◽

C2a Domain

Abstract Synaptic vesicle (SV) exocytosis is mediated by SNARE proteins. Reconstituted SNAREs are constitutively active, so a major focus has been to identify fusion clamps that regulate their activity in synapses: the primary candidates are synaptotagmin (syt) 1 and complexin I/II. Syt1 is a Ca2+ sensor for SV release that binds Ca2+ via tandem C2-domains, C2A and C2B. Here, we first determined whether these C2-domains execute distinct functions. Remarkably, the C2B domain profoundly clamped all forms of SV fusion, despite synchronizing residual evoked release and rescuing the readily-releasable pool. Release was strongly enhanced by an adjacent C2A domain, and by the concurrent binding of complexin to trans-SNARE complexes. Knockdown of complexin had no impact on C2B-mediated clamping of fusion. We postulate that the C2B domain of syt1, independent of complexin, is the molecular clamp that arrests SVs prior to Ca2+-triggered fusion.

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