Myosin Light Chain Kinase Is Not a Regulator of Synaptic Vesicle Trafficking during Repetitive Exocytosis in Cultured Hippocampal Neurons

Tokuoka, Hirofumi; Goda, Yukiko

doi:10.1523/jneurosci.3400-06.2006

Cited by 36 publications

(40 citation statements)

References 48 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Second, stimulation-induced mobility is unaffected by depolymerizing F-actin. Along with other experiments (Silverman et al, 2005;Gaffield et al, 2006;Tokuoka and Goda, 2006), this finding suggests that the long-standing question of whether F-actin is a barrier for vesicle immobilization or a track for motor-mediated translocation (Nunes et al, 2006;Scalettar, 2006) is not central to understanding stimulation-induced vesicle motion. Finally, the stimuli in each case are associated with Ca 2ϩ influx, which was explicitly demonstrated to be required for enhancing vesicle mobility in two of the studies (Shakiryanova et al, 2005;Allersma et al, 2006).…”

Section: Introductionmentioning

confidence: 63%

Presynaptic Ryanodine Receptor-Activated Calmodulin Kinase II Increases Vesicle Mobility and Potentiates Neuropeptide Release

Shakiryanova¹,

Klose²,

Zhou³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Although it has been postulated that vesicle mobility is increased to enhance release of transmitters and neuropeptides, the mechanism responsible for increasing vesicle motion in nerve terminals and the effect of perturbing this mobilization on synaptic plasticity are unknown. Here, green fluorescent protein-tagged dense-core vesicles (DCVs) are imaged in Drosophila motor neuron terminals, where DCV mobility is increased for minutes after seconds of activity. Ca 2ϩ -induced Ca 2ϩ release from presynaptic endoplasmic reticulum (ER) is shown to be necessary and sufficient for sustained DCV mobilization. However, this ryanodine receptor (RyR)-mediated effect is short-lived and only initiates signaling. Calmodulin kinase II (CaMKII), which is not activated directly by external Ca 2ϩ influx, then acts as a downstream effector of released ER Ca 2ϩ . RyR and CaMKII are essential for post-tetanic potentiation of neuropeptide secretion. Therefore, the presynaptic signaling pathway for increasing DCV mobility is identified and shown to be required for synaptic plasticity.

show abstract

Section: Introductionmentioning

confidence: 63%

Presynaptic Ryanodine Receptor-Activated Calmodulin Kinase II Increases Vesicle Mobility and Potentiates Neuropeptide Release

Shakiryanova¹,

Klose²,

Zhou³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…FM1-43 is a useful tool to study synaptic vesicle recycling (27,28), enabling the tracking of single synaptic vesicle dynamics (3, …”

Section: Discussionmentioning

confidence: 99%

Activity-dependent coordination of presynaptic release probability and postsynaptic GluR2 abundance at single synapses

Tokuoka

Goda

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The strength of an excitatory synapse depends on both the presynaptic release probability (p r) and the abundance of functional postsynaptic AMPA receptors. How these parameters are related or balanced at a single synapse remains unknown. By taking advantage of live fluorescence imaging in cultured hippocampal neurons where individual synapses are readily resolved, we estimate p r by labeling presynaptic vesicles with a styryl dye, FM1-43, while concurrently measuring postsynaptic AMPA receptor abundance at the same synapse by immunolabeling surface GluR2. We find no appreciable correlation between pr and the level of surface synaptic GluR2 under basal condition, and blocking basal neural activity has no effect on the observed lack of correlation. However, elevating network activity drives their correlation, which accompanies a decrease in mean GluR2 level. These findings provide the direct evidence that the coordination of pre-and postsynaptic parameters of synaptic strength is not intrinsically fixed but that the balance is tuned by synaptic use at individual synapses.hippocampal culture ͉ synaptic strength ͉ FM1-43 ͉ neurotransmitter release ͉ glutamate receptor I n the classical Katz model of synaptic transmission, the weight of each synapse is determined by p r and quantal size (q), as p r ϫ q (1, 2). Because q is largely governed by postsynaptic receptors, synapses have to regulate both pre-and postsynaptic mechanisms to control the overall synaptic strength. Across a population of synapses, p r (3) and postsynaptic receptor level (4) are highly heterogeneous. Therefore, it is of fundamental importance to identify how the relationship between pre-and postsynaptic strengths at individual synapses is organized. For instance, the balance between the two could be compensative, synergistic, or random. Amongst a synapse population, compensative balance would result in relatively uniform synaptic strengths. In contrast, synergistic balance would result in a biased or skewed distribution of synaptic strengths. Thus, the manner in which preand postsynaptic strengths are balanced might influence dendritic processing and operation of neural networks.Previous studies on synaptic structure and physiology suggest for a positive correlation between p r and postsynaptic surface AMPA receptor level. For example, the number of AMPA receptors is correlated to postsynaptic density (PSD) size (5, 6), which, in turn, is matched to the presynaptic active zone length (7). Also, a larger presynaptic active zone supports a larger pool of readily releasable synaptic vesicles, resulting in higher p r (8,9). In further support of the view that p r and postsynaptic surface AMPA receptor abundance are correlated, overexpression of postsynaptic proteins such as PSD-95, Shank, or GluR2 enhances AMPA receptor clustering and increases spine size, and these postsynaptic changes are, in turn, accompanied by enhanced presynaptic release (10-12). Nevertheless, beyond these reports, no studies to date have directly addressed how p r and postsyna...

show abstract

“…MLCK has been suggested to mediate the mobilization of synaptic vesicles (SVs) in the reserve pool at the NMJ (Verstreken et al, 2005), but its role at hippocampal synapse is controversial (Ryan, 1999;Tokuoka and Goda, 2006). To test the involvement of MLCK in posttetanic change of the RRP size, we studied the effects of ML-7, a specific MLCK inhibitor, on PTP and TSinduced increase in the RRP size.…”

Section: Mlck Inhibitors Abolish Specifically the Posttetanic Increasmentioning

confidence: 99%

Presynaptic Release Probability and Readily Releasable Pool Size Are Regulated by Two Independent Mechanisms during Posttetanic Potentiation at the Calyx of Held Synapse

Lee¹,

Kim²,

Ho³

et al. 2008

J. Neurosci.

118

View full text Add to dashboard Cite

At the immature calyx of Held, the fast decay phase of a Ca 2ϩ transient induced by tetanic stimulation (TS) was followed by a period of elevated [Ca 2ϩ ] i for tens of seconds, referred to as posttetanic residual calcium (Ca res ). We investigated the source of Ca res and its contribution to posttetanic potentiation (PTP). After TS (100 Hz for 4 s), posttetanic Ca res at the calyx of Held was largely abolished by tetraphenylphosphonium (TPP ϩ ) or Ru360, which inhibit mitochondrial Na ϩ -dependent Ca 2ϩ efflux and Ca 2ϩ uniporter, respectively. Whereas the control PTP lasted longer than Ca res , inhibition of Ca res by TPP ϩ resulted in preferential suppression of the early phase of PTP, the decay time course of which well matched with that of Ca res . TS induced significant increases in release probability (P r ) and the size of the readily releasable pool (RRP), which were estimated from plots of cumulative EPSC amplitudes. TPP ϩ or Ru360 suppressed the posttetanic increase in P r , whereas it had little effect on the increase in RRP size. Moreover, the posttetanic increase in P r , but not in RRP size, showed a linear correlation with the amount of Ca res . In contrast, myosin light chain kinase (MLCK) inhibitors and blebbistatin reduced the posttetanic increase in RRP size with no effect on the increase in P r . Application of TPP ϩ in the presence of MLCK inhibitor peptide caused further suppression of PTP. These findings suggest that Ca res released from mitochondria and activation of MLCK are primarily responsible for the increase in P r and that in the RRP size, respectively.

show abstract

Myosin Light Chain Kinase Is Not a Regulator of Synaptic Vesicle Trafficking during Repetitive Exocytosis in Cultured Hippocampal Neurons

Cited by 36 publications

References 48 publications

Presynaptic Ryanodine Receptor-Activated Calmodulin Kinase II Increases Vesicle Mobility and Potentiates Neuropeptide Release

Presynaptic Ryanodine Receptor-Activated Calmodulin Kinase II Increases Vesicle Mobility and Potentiates Neuropeptide Release

Activity-dependent coordination of presynaptic release probability and postsynaptic GluR2 abundance at single synapses

Presynaptic Release Probability and Readily Releasable Pool Size Are Regulated by Two Independent Mechanisms during Posttetanic Potentiation at the Calyx of Held Synapse

Contact Info

Product

Resources

About