EC:2.7.11.13 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: EC:2.7.11.13 (protein kinase C)
49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms underlying short-term presynaptic facilitation, the enhancement of transmitter release from sensory neurons in Aplysia, induced by serotonin (5-HT), can be divided into two categories: (1) changes in ionic conductances leading to spike broadening and enhancement of Ca2+ influx; and (2) actions on the machinery for transmitter release that are independent of spike broadening and the resulting increases in Ca2+ influx. Spike broadening and the associated enhancement of excitability are induced by the modulation of K+ conductances in the sensory neuron. The cellular mechanisms that contribute to the enhancement of release that is independent of spike broadening are not known and may involve vesicle mobilization or other steps in exocytotic release. These two facilitatory actions of 5-HT are mediated by at least two second-messenger-activated protein kinase systems, protein kinase A (PKA) and protein kinase C (PKC). These two second-messenger cascades overlap in their contributions to synaptic facilitation. However, their relative contributions to enhancement of transmitter release are not simply synergistic but are state- and time-dependent. The state dependence is a reflection of the synapse's previous history of activity. When the synapse is rested (and not depressed), a brief pulse of 5-HT (lasting from 10 sec to 5 min) produces its actions primarily through PKA via both spike broadening-dependent and -independent mechanisms. The broadening primarily involves the modulation of a voltage-dependent K+ current, IKV, with a small contribution by a voltage-independent K+ current, IKS. By contrast, the enhancement of excitability is mediated primarily by the modulation of IKS. As the synapse becomes depressed with repeated activity, the contribution of PKC becomes progressively more important. As is the case with PKA, PKC produces its action both by broadening the spike via modulation of IKV and by a spike broadening-independent mechanism. In addition to being state-dependent, the mechanisms of facilitation are time-dependent. There are differences in the response to 5-HT when it is given briefly to produce short-term facilitation or when the exposure is prolonged. When exposure is brief (< or = 5 min), PKA dominates. When exposure is prolonged (10-20 min), PKC becomes dominant as it is with depressed synapses. Thus, synaptic plasticity appears to be expressed in several overlapping time domains, and the transition between very short-term facilitation and various intermediate duration phases seems to involve interactive processes between the kinases.
...
PMID:Presynaptic facilitation revisited: state and time dependence. 855 27

An overview of some of the biochemical and molecular events involved in the process of learning and memory are presented in a short review. Two invertebrate models of learning are considered: the gill-withdrawal reflex of Aplysia and avoidance learning in Drosophila melanogaster. Particular attention is paid to the biochemical mechanisms underlying both the development of long-term potentiation (LTP) and passive avoidance learning (PAL) in the young chick. The role of several biological molecules in learning and memory are considered, for example, protein kinase C (PKC), Ca(++)-Calmodulin kinase II (CaMKII), GAP-43, and glutamate receptors.
...
PMID:The biochemistry of learning and memory. 856 41

The Aplysia nervous system contains two phorbol ester-activated protein kinase C isoforms, the Ca(2+)-activated Apl I and the Ca(2+)-independent Apl II. Short-term applications of the facilitatory transmitter serotonin (5-HT) activates Apl I, but not Apl II. In contrast, Apl II, but not Apl I, can form an autonomous kinase. To investigate the biochemical characteristics of the Aplysia kinases that might underlie their differential activation, we expressed Apl I, Apl II, and two derivatives of Apl II with deletions in the amino-terminal 150 amino acid E region in insect cells using the baculovirus system. Similar to nervous system extracts, expressed Apl II has more autonomous activity than Apl I. Removal of the E region lowered the amount of phosphatidylserine required for activation of Apl II, but did not remove the autonomous kinase activity. In addition, phosphatidylserine vesicles could sediment fusion proteins containing the E region, consistent with a role for the E region in lipid interactions. A partial deletion of the E region modifies activation of Apl II by phorbol esters and oleic acid, suggesting that in the intact enzyme the E region interacts with the phorbol ester-binding domain of the kinase. These results introduce a model whereby the E region acts as a negative regulator of Apl II activation and suggest that this inhibition may explain the inability of short-term applications of 5-HT to activate Apl II.
...
PMID:Expression and characterization of Aplysia protein kinase C: a negative regulatory role for the E region. 861 75

Activation of tyrosine kinase-linked receptors has been shown to stimulate Ca2+-independent protein kinase C isoforms in nonneuronal cells. We have examined this signaling pathway in the nervous system. Incubating bag cell neurons from the marine mollusk Aplysia californica with concentrations of insulin known to stimulate a tyrosine kinase-linked receptor in these cells persistently activated and down-regulated the Ca2+-independent protein kinase C (Apl II), whereas insulin only transiently activated and did not down-regulate the Ca2+-activated protein kinase C (Apl I). The effects of insulin may be mediated by activation of phosphoinositide 3-kinase because (a) diC16phosphatidylinositol 3,4,5-trisphosphate, a synthetic phosphoinositide 3-kinase product, stimulated autophosphorylation of baculovirus-expressed Apl II, but not of Apl I, and (b) wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked the activation and down-regulation of Apl II by insulin but not the transient activation of Apl I. These results suggest that activators of tyrosine kinase-linked receptors may mediate some of their effects in neurons through activation of Ca2+-independent protein kinase C isoforms.
...
PMID:Stimulation of an insulin receptor activates and down-regulates the Ca2+-independent protein kinase C, Apl II, through a Wortmannin-sensitive signaling pathway in Aplysia. 866 95

The effect of elevated PKC activity on the membrane depolarization (D-response) evoked by extracellular ACh, applied on the soma of Aplysia neurons, was studied. Intracellularly injected PKC and certain PKC activators were used to elevate PKC activity. ACh-induced current was measured in voltage clamp. The neurons were treated extracellularly with the PKC activators: PDAc, SC-10, R-59949, (-)-ILV; or with purified PKC injected into the neuron through the recording electrode. PKC injection and treatment with any of the PKC activators caused a similar reduction of the ACh-induced inward Na current response (corresponding to D-response), while the non-activating alpha-PDD had no effect. The results provide evidence that a PKC-dependent reduction of receptor responses also exists in this kind of Aplysia neurons. Furthermore, they show that the reduction of ACh response is indeed due to PKC activation (and not to a direct action of the phorbol ester).
...
PMID:PKC-dependent reduction of the acetylcholine-evoked inward Na current in Aplysia D-neurons: effect of injected PKC and PKC activators. 872 Aug 67

1. The sensorimotor synapse of Aplysia expresses various shortlasting changes in synaptic efficacy including homosynaptic depression (HSD) and heterosynaptic facilitation by serotonin (5-HT) either at nondepressed sensory neuron (SN) synaptic connections or at SN synaptic connections first depressed by HSD. We examined the temporal sequence of expression for these three forms of synaptic plasticity as synaptic connections between SN and target motor cell L7 were reestablished and stabilized in cell culture. The same cultures were reexamined at different time points. 2. We found that only HSD and facilitation of nondepressed synapses were expressed at "mature" levels on day 1 in culture, whereas facilitation of depressed connections was significantly weaker on day 1 than the facilitation evoked on day 4. 3. The late expression of 5-HT facilitation of depressed SN synaptic connections was not a result of a reduced capacity of two kinases activated by 5-HT (protein kinase A and protein kinase C) to evoke facilitation. Direct activation of the kinases with either cyclic AMP or phorbol esters evoked the synaptic facilitation both on day 1 and day 4. 4. The late expression of 5-HT facilitation of depressed SN synaptic connections was correlated with the late functional expression of receptors sensitive to 5-HT antagonists cyproheptidine or methiothepin. Both antagonists significantly interfered with 5-HT facilitation on day 4, but both had little effect on 5-HT facilitation of the same cultures examined on day 1. 5. Unlike the properties of SNs in the intact nervous system, both antagonists reduced significantly the excitability changes evoked by 5-HT when the SNs were plated either alone or with target cell L11 that fails to induce synapse formation. When cultured with L7, however, both antagonists evoked little change in 5-HT excitability. In the presence of L7, the SNs expressed the phenotype more typical of SNs in the intact nervous system. 6. The results suggest that target interactions not only influence the formation of chemical connections but they also may regulate the acquisition of specific plastic properties by the presynaptic neuron including the functional expression of receptors for neuromodulators.
...
PMID:Development of short-term heterosynaptic facilitation at aplysia sensorimotor synapses in vitro is accompanied by changes in the functional expression of presynaptic serotonin receptors. 889

We have investigated the developmental regulation of the ability to fire repetitively in the bag cell neurons of Aplysia californica, a neuronal system in which the behavioral effects of repetitive firing are well characterized. Adult bag cell neurons exhibit an afterdischarge, consisting of prolonged depolarization and repetitive firing, which causes the release of several peptides from these neurons that induce egg-laying behaviors. Afterdischarge can be triggered in vitro by a variety of stimuli, including electrical stimulation and exposure to the potassium channel blocker tetraethyl ammonium chloride (TEA). In contrast to adults, juvenile neurons did not exhibit afterdischarge in response to pleural-abdominal connective shock or TEA. Juvenile neurons did exhibit, however, prolonged depolarizations in the presence of TEA, perhaps reflecting the anlage of the mechanism responsible for afterdischarge in the adult. To investigate developmental mechanisms underlying the regulation of repetitive firing, we compared ionic currents in adult and juvenile bag cell neurons. We found that during the period in which these neurons acquire the capacity to fire repetitively, a number of currents are regulated: (1) three K+ currents decrease (Ca2+)-dependent K+ and two components of voltage-dependent delayed-rectifier K+ current); (2) A-type K+ current increases; and (3) two Ca2+ currents increase (basal and PKC-activated). This pattern is consistent with the increase in the ability to fire repetitively that we observe during maturation: our results indicate that developmental control of repetitive firing in this system is accompanied by selective regulation of specific ionic currents which, after maturation, play important roles in generating the afterdischarge and triggering egg-laying behaviors.
...
PMID:Ionic currents underlying developmental regulation of repetitive firing in Aplysia bag cell neurons. 892 15

To study the molecular mechanism of calcium current modulation in the bag cell neurons of Aplysia californica, we have identified calcium channel subtypes expressed in these cells and analyzed their distribution using channel-specific antibodies. Using PCR to amplify reverse-transcribed RNA from bag cell clusters, we identified two classes of calcium channel alpha1 subunit. One, BCCa-I, belongs to the ABE subfamily of calcium channels, whereas the other, BCCa-II, belongs to the SCD subfamily. Antibodies generated against the bag cell calcium channels recognize membrane proteins of approximately 210 and 280 kDa on immunoblots. Both channels are expressed in the bag cell clusters as well as in other parts of the Aplysia nervous system. BCCa-II also localizes to glia and muscle. The subcellular distribution of the two channel types is strikingly different. Antibody staining of bag cell neurons in primary culture shows that BCCa-II is present on the plasma membrane, whereas BCCa-I has a punctate, intracellular distribution consistent with a vesicular localization. The BCCa-I-containing vesicles are found in bag cell neuron somata and growth cones and occasionally in neuritic hotspots. Their distribution is similar but not identical to that of LysoTracker Red, a marker for acidic organelles, but unlike that of dense-core vesicles containing egg-laying hormone. The vesicular channels may represent the protein kinase C-sensitive calcium channels of bag cell neurons that are believed to enhance hormonal release during electrical activity.
...
PMID:Identification of a vesicular pool of calcium channels in the bag cell neurons of Aplysia californica. 903 Jun 18

The effect of altered protein kinase C (PKC) activity level on the synaptic transmission in the central ganglia of Aplysia californica was studied. EPSPs or EPSCs evoked in the postsynaptic neuron by presynaptic nerve stimulation were recorded while the ganglion was in vitro treated with PKC activators (phorbol diacetate and SC-10) or PKC blockers (H-7, sphingosine, Cremophor-EL). It was found that the postsynaptic reaction was enhanced by increased and reduced by decreased PKC activity and that this modulatory influence of PKC was presynaptic.
...
PMID:Presynaptic modification of synaptic transmission at identified Aplysia central synapses, induced by changes in protein kinase C activity. 904 46

Serotonergic modulation of sensory neurons in Aplysia and their synaptic connections with follower cells has been used extensively as a model system with which to study mechanisms underlying neuronal plasticity. Serotonin (5-HT)-induced facilitation of sensorimotor connections is due to at least two processes: a process related to the broadening of presynaptic action potentials and a spike-duration-independent (SDI) process that may involve mobilization of transmitter. We have examined the relationship between spike broadening and synaptic facilitation of relatively nondepressed sensorimotor connections in the intact pleural-pedal ganglia. Previously, 5-HT-induced spike broadening in the sensory neuron was shown to be primarily due to the modulation of a voltage-dependent K+ current (Ik.v). Low concentrations (20-30 microM) of 4-aminopyridine (4-AP) were used to rather selectively block Ik.v. 4-AP increased spike duration in the sensory neuron and the excitatory postsynaptic potential (EPSP) in the motor neuron. The temporal development of 4-AP-induced spike broadening closely parallel that of synaptic facilitation. Thus spike broadening via the reduction of Ik.v can directly contribute to synaptic facilitation. The relationship between spike broadening induced by 5-HT (10 microM) and enhancement of the EPSP was also analyzed. We found that components of 5-HT-induced synaptic facilitation preceded the development of 5-HT-induced spike broadening. The comparison between the results of 4-AP and 5-HT revealed that the SDI processes made an important contribution to the rapid development of 5-HT-induced synaptic facilitation and that spike broadening made an important contribution to its maintenance. The SDI process and a slowly developing component of 5-HT-induced spike broadening are mediated, at least in part, by the activation of protein kinase C (PKC). Application of phorbol 12,13-diacetate (PDAc), an activator of PKC, partially mimicked the effects of 5-HT on spike duration and the EPSP. PDAc-induced enhancement of the EPSP preceded the slower development of PDAc-induced spike broadening. Like 5-HT, PDAc enhanced the EPSP via both spike broadening and the SDI processes. In addition, a 15-min exposure to PDAc occluded 5-HT-induced enhancement of the EPSP, suggesting that PKC and 5-HT engage similar or overlapping mechanisms. On the basis of these results and others, we propose a time-dependent hypothesis for the 5-HT-induced synaptic facilitation of nondepressed synapses, in which multiple second-messenger/protein kinase systems mediate the actions of 5-HT via both spike-duration-dependent and SDI processes.
...
PMID:Differential effects of 4-aminopyridine, serotonin, and phorbol esters on facilitation of sensorimotor connections in Aplysia. 912 May 59

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>