Calcium-Dependent PKC Isoforms Have Specialized Roles in Short-Term Synaptic Plasticity

Chu, YunXiang; Fioravante, Diasynou; Leitges, Michael; Regehr, Wade G.

doi:10.1016/j.neuron.2014.04.003

Cited by 38 publications

(52 citation statements)

References 85 publications

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“…PKC is inhibited by mood stabilizers such as lithium and valproic acid [14]. Additionally, PKC signaling is involved in the regulation of processes that are affected in BD, such as neuronal excitability [23], neurotransmitter release [24,25], glutamatergic neurotransmission [26], neuroplasticity [27], apoptotic pathway activation [28], mitochondrial dysfunction, and oxidative stress [29], and neuroinflammation [30,31,32]. …”

Section: Introductionmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.

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Section: Introductionmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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“…The large extent and the long duration of mossy fiber PTP in comparison to other synapses (Chu et al, 2014; Habets and Borst, 2007; Korogod et al, 2005) suggest that the switch from subdetonation to full detonation may be exquisitely relevant for the function of the hippocampal network in vivo . The activity dependence of PTP at different synapses is not precisely known.…”

Section: Discussionmentioning

confidence: 99%

Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses

Vyleta

Borges-Merjane

Jónás

2016

eLife

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Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network.DOI: http://dx.doi.org/10.7554/eLife.17977.001

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“…For instance, activated cPKCs amplify and sustain NT release that accounts for presynaptic plasticity in auditory and cerebellar synapses (13)(14)(15). In a model of auditory learning and information processing, PKC␥ upregulates NT release during early development; PKC␤ promotes NT release at the same synapse in mature animals.…”

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A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

Land

Rubin

2017

Molecular and Cellular Biology

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Ca 2ϩ -and diacylglycerol (DAG)-activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a Caenorhabditis elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (T c ) and migrates along the T c within a 17 to 25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2 Ϫ/Ϫ animals. Cell-specific manipulation of PKC-2 activity revealed that thermotaxis is controlled by cooperative PKC-2-mediated signaling in both AFD sensory neurons and intestinal cells. Cold-directed migration (cryophilic drive) precedes T c tracking during thermotaxis. Analysis of temperature-directed behaviors elicited by persistent PKC-2 activation or inhibition in AFD (or intestine) disclosed that PKC-2 regulates initiation and duration of cryophilic drive. In AFD neurons, PKC-2 is a Ca 2ϩ sensor and signal amplifier that operates downstream from cyclic GMP-gated cation channels and distal guanylate cyclases. UNC-18, which regulates neurotransmitter and neuropeptide release from synaptic vesicles, is a critical PKC-2 effector in AFD. UNC-18 variants, created by mutating Ser 311 or Ser 322 , disrupt thermotaxis and suppress PKC-2-dependent cryophilic migration.KEYWORDS C. elegans signal integration, MUNC18 and UNC-18, calcium, diacylglycerol-activated PKC, cyclic GMP-gated channel, protein kinase C, regulation of learned behavior, sensory neuron, signal transduction, thermotaxis D iacylglycerol (DAG) and free cytoplasmic Ca 2ϩ mediate actions of hormones, neurotransmitters (NTs), and other stimuli that activate phospholipases C␤ and C␥ (1). Conventional protein kinase C isoforms (cPKCs ␣, ␤I, ␤II, and ␥) are widely expressed effectors of Ca 2ϩ and DAG in mammalian tissues (2-5). cPKCs are translocated to membranes and activated by binding Ca 2ϩ and DAG via their respective C2 and C1 domains. Thus, cPKCs are poised to receive, amplify, and disseminate the complete spectrum of intracellular signals generated by phospholipase C activation. Accordingly, cPKCs often couple extracellular stimuli to physiological processes that are coregulated by dynamic changes in Ca 2ϩ and DAG levels. In contrast, novel PKC isoforms (nPKCs ␦, , , and ) are activated by DAG alone.Some cell functions are redundantly regulated by combinations of PKCs. However, individual cPKCs can control key aspects of homeostasis or, when misregulated, promote pathological processes. For example, PKC␣ selectively regulates cardiac contrac-

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Calcium-Dependent PKC Isoforms Have Specialized Roles in Short-Term Synaptic Plasticity

Cited by 38 publications

References 85 publications

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses

A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

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