Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal

Saitoh, Naoto; Hori, Tomohide; Takahashi, Tomoyuki

doi:10.1073/pnas.241333598

Cited by 53 publications

(52 citation statements)

References 45 publications

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“…As increased phosphorylation of S279 reflects an increase in the amount of PKCe that can be fully activated by lipid second messengers (Saitoh et al, 2001;Bayer et al, 2003;Zhou et al, 2003;Olive et al, 2005), these results suggest that ethanol stimulates a signaling cascade that increases the pool size of fully phosphorylated PKCe in the cerebellum. Although ethanol-stimulated PKCe phosphorylation at S729 in wildtype mice, we were only able to measure this increase 60 min following ethanol injection and not at 30 min or earlier time points.…”

Section: Discussionmentioning

confidence: 80%

“…Phosphorylation at S729 permits full activity of PKCe when the enzyme is stimulated by lipid second messengers (Parekh et al, 1999;Takahashi et al, 2000). Thus, PKCe phosphorylation at S729 has been used as a marker for activation and posttranslational processing of the immature pool of PKCe that is not yet fully phosphorylated (Saitoh et al, 2001;Bayer et al, 2003;Zhou et al, 2003;Olive et al, 2005). Therefore, we used a phospho-specific antibody that detects phosphorylation of PKCe at S729 to investigate the regulation of the immature PKCe pool by ethanol.…”

Section: Ethanol Treatment Increases Pkce S729 Phosphorylation In Thementioning

confidence: 99%

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Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Wallace

Newton

Oyasu

et al. 2006

Neuropsychopharmacol

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A low level of response to ethanol is associated with increased risk of alcoholism. A major determinant of the level of response is the capacity to develop acute functional tolerance (AFT) to ethanol during a single drinking session. Mice lacking protein kinase C epsilon (PKCe) show increased signs of ethanol intoxication and reduced ethanol self-administration. Here, we report that AFT to the motorimpairing effects of ethanol is reduced in PKCe (À/À) mice when compared with wild-type littermates. In wild-type mice, in vivo ethanol exposure produced AFT that was accompanied by increased phosphorylation of PKCe and resistance of GABA A receptors to ethanol. In contrast, in PKCe (À/À) mice, GABA A receptor sensitivity to ethanol was unaltered by acute in vivo ethanol exposure. Both PKCe (À/À) and PKCe ( + / + ) mice developed robust chronic tolerance to ethanol, but the presence of chronic tolerance did not change ethanol preference drinking. These findings suggest that ethanol activates a PKCe signaling pathway that contributes to GABA A receptor resistance to ethanol and to AFT. AFT can be genetically dissociated from chronic tolerance, which is not regulated by PKCe and does not alter PKCe modulation of ethanol preference.

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Section: Discussionmentioning

confidence: 80%

Section: Ethanol Treatment Increases Pkce S729 Phosphorylation In Thementioning

confidence: 99%

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Wallace

Newton

Oyasu

et al. 2006

Neuropsychopharmacol

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“…It has been reported that actin filaments are abundant, intermixed with synaptic vesicles (10), and are present along the presynaptic membrane at the calyx of Held (11). Depolymerization of actin filaments suppresses the recovery of releasable SVs after depletion (12).…”

Section: Recovery Of Rapidly Releasing Vesicles After a Predepletingmentioning

confidence: 99%

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Lee

2012

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

105

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Glutamatergic synaptic terminals harbor reluctant synaptic vesicles (SVs) that contribute little to synchronous release during action potentials but are release competent when stimulated by sucrose or by direct intracellular application of calcium. It has been noted that the proximity of a release-competent SV to the calcium source is one of the primary factors that differentiate reluctant SVs from fastreleasing ones at the calyx of Held synapse. It has not been known whether reluctant SVs can be converted into fast-releasing ones. Here we show that reluctant SVs are recruited rapidly in an actindependent manner to become fast-releasing SVs once the pool of fast-releasing SVs is depleted by a short depolarization. Recovery of the pool of fast-releasing SVs was accompanied by a parallel reduction in the number of reluctant SVs. Quantitative analysis of the time course of depletion of fast-releasing SVs during high-frequency stimulation revealed that in the early phase of stimulation reluctant SVs are converted rapidly into fast-releasing ones, thereby counteracting short-term depression. During the late phase, however, after reluctant vesicles have been used up, another process of calmodulindependent recruitment of fast-releasing SVs is activated. These results document that reluctant SVs have a role in short-term plasticity and support the hypothesis of positional priming, which posits that reluctant vesicles are converted into fast-releasing ones via relocation closer to Ca 2+ -channels.readily releasable pool | synaptic vesicle dynamics S ynaptic strength is determined by quantal size, the number of release-competent synaptic vesicles (SVs), and their release probability (Pr). The estimate for the number of release-competent SVs, which also is referred to as the "readily releasable pool (RRP) size," depends heavily on the method used for its determination. The RRP size estimated by a cumulative plot of the excitatory postsynaptic currents (EPSC) amplitudes evoked by high-frequency afferent fiber stimulation (RRP cum ) is smaller than that estimated by the application of a hypertonic sucrose solution or presynaptic strong depolarization (1-3). This discrepancy reflects the presence of reluctant SVs, which are scarcely released by an action potential (AP) at glutamatergic synaptic terminals. Consistently, deconvolution analysis of EPSCs evoked by a long depolarizing pulse at the calyx of Held revealed that release-competent SVs can be separated into fast-and slowreleasing SV pools (FRP and SRP, respectively) (4). The FRP vesicles are responsible for phasic release during a high-frequency train of action potentials (APs), whereas the SRP vesicles contribute primarily to asynchronous release, when the intracellular concentration of calcium ions ([Ca 2+ ]) is increased globally during the late period of the train (2). Thus, SRP vesicles can be regarded largely as reluctant SVs at the calyx of Held.Despite the evidence for the presence of reluctant SVs at glutamatergic synapses, their role in short-term plasticity i...

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“…Modulatory effects on quantal release can be examined in isolation while the terminal is voltage clamped and presynaptic membrane currents are monitored. Phalloidin staining showed that F-actin is confined to the distal end of the presynaptic terminal of the calyx of Held (Saitoh et al, 2001).…”

Section: Nem and Staurosporine Do Not Affect Recruitment Of Releasablmentioning

confidence: 99%

“…It is therefore unlikely that the effect of ATP-␥S is caused by activation of protein kinases. Phorbol esters, activators of protein kinase C, seem ineffective in modulating the recovery from vesicle pool depletion at the calyx synapse , although activation of PKC and the actin cytoskeleton are somehow related (Saitoh et al, 2001). …”

Section: Roles Of Nsf and Protein Kinases In Vesicle Recruitmentmentioning

confidence: 99%

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

2003

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Depletion and replenishment of pools of synaptic vesicles are important determinants of short-term synaptic plasticity, but the underlying molecular mechanisms are not yet clear. As a first step toward understanding the process of vesicle recruitment, we have applied various specific agents directly to the presynaptic terminal of the calyx of Held synapse. Here we show that the nonhydrolyzable ATP analog ATP-␥S retards the recovery from vesicle pool depletion, as does latrunculin A. Phalloidin has no effects on recovery, suggesting that dynamic actin reorganization is not necessary. Unexpectedly, neither N-ethylmaleimide nor staurosporine affected the recovery, calling into question the role of N-ethylmaleimide-sensitive factor and protein kinases. The results suggest that intact actin polymerization is involved in vesicle recruitment.

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Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal

Cited by 53 publications

References 45 publications

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

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