scholarly journals The Ras-like GTPase Rem2 is a potent endogenous inhibitor of calcium/calmodulin-dependent kinase II activity

2017 ◽  
Author(s):  
Leandro Royer ◽  
Josiah J. Herzog ◽  
Katelyn Kenny ◽  
Boriana Tzvetkova ◽  
Jesse C. Cochrane ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Catalytic Domain ◽  
Physiological Role ◽  
Long Term Potentiation ◽  
Endogenous Inhibitor ◽  
Calcium Calmodulin Dependent ◽  
Term Potentiation ◽  
Cellular Context ◽  
Activity Dependent

AbstractCaMKII is a well-characterized, abundant protein kinase that regulates a diverse set of functions in a tissue specific manner. For example, in heart muscle, CaMKII regulates Ca2+ homeostasis while in neurons CaMKII regulates activity-dependent dendritic remodeling and Long Term Potentiation (LTP), a biological correlate of learning and memory. Previously, we identified the noncanonical GTPase Rem2 as a critical regulator of dendrite branching and synapse formation in the vertebrate nervous system. Here, we report that Rem2 directly interacts with CaMKII and potently inhibits the activity of the intact holoenzyme, a previously undescribed function for the Rem2 protein. To date, only one other endogenous inhibitor of CaMKII has been described: CaMKIIN, which blocks CaMKII activity through binding to the catalytic domain. Our data suggest that Rem2 inhibits CaMKII through a novel mechanism, as inhibition requires the presence of the association domain of CaMKII. Our biochemical finding that Rem2 is a direct, endogenous inhibitor of CaMKII activity, coupled with known functions of Rem2 in neurons, provides a framework which will enable future experiments probing the physiological role of CaMKII inhibition in a cellular context.

scholarly journals SCAMP5 mediates activity-dependent enhancement of NHE6 recruitment to synaptic vesicles during synaptic plasticity

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Unghwi Lee ◽  
Seung Hyun Ryu ◽  
Sunghoe Chang
Keyword(s):  
Synaptic Plasticity ◽  
Synapse Formation ◽  
Glutamate Release ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Quantal Size ◽  
Term Potentiation ◽  
Presynaptic Boutons ◽  
Activity Dependent

AbstractNa+(K+)/H+ exchanger 6 (NHE6) on synaptic vesicle (SV) is critical for the presynaptic regulation of quantal size at the glutamatergic synapses by converting the chemical gradient (ΔpH) into membrane potential (Δψ) across the SV membrane. We recently found that NHE6 directly interacts with secretory carrier membrane protein 5 (SCAMP5), and SCAMP5-dependent recruitment of NHE6 to SVs controls the strength of synaptic transmission by modulation of quantal size of glutamate release at rest. It is, however, unknown whether NHE6 recruitment by SCAMP5 plays a role during synaptic plasticity. Here, we found that the number of NHE6-positive presynaptic boutons was significantly increased by the chemical long-term potentiation (cLTP). Since cLTP involves new synapse formation, our results indicated that NHE6 was recruited not only to the existing presynaptic boutons but also to the newly formed presynaptic boutons. Knock down of SCAMP5 completely abrogated the enhancement of NHE6 recruitment by cLTP. Interestingly, despite an increase in the number of NHE6-positive boutons by cLTP, the quantal size of glutamate release at the presynaptic terminals remained unaltered. Together with our recent results, our findings indicate that SCAMP5-dependent recruitment of NHE6 plays a critical role in manifesting presynaptic efficacy not only at rest but also during synaptic plasticity. Since both are autism candidate genes, reduced presynaptic efficacy by interfering with their interaction may underlie the molecular mechanism of synaptic dysfunction observed in autism.

The Vertical Lobe of Cephalopods

2017 ◽  
pp. 558-574 ◽  
Author(s):  
Ana Turchetti-Maia ◽  
Tal Shomrat ◽  
Binyamin Hochner
Keyword(s):  
Complex Networks ◽  
Long Term Potentiation ◽  
Learning Networks ◽  
Neuronal Circuitry ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Matrix Organization ◽  
Activity Dependent ◽  
Similar Organization

We show that the cephalopod vertical lobe (VL) is a promising system for assessing the function and organization of the neuronal circuitry mediating complex learning and memory behavior. Studies in octopus and cuttlefish VL networks suggest an independent evolutionary convergence into a matrix organization of a divergence-convergence (“fan-out fan-in”) network with activity-dependent long-term plasticity mechanisms. These studies also show, however, that the properties of the neurons, neurotransmitters, neuromodulators, and mechanisms of induction and maintenance of long-term potentiation are different from those evolved in vertebrates and other invertebrates, and even highly variable among these two cephalopod species. This suggests that complex networks may have evolved independently multiple times and that, even though memory and learning networks share similar organization and cellular processes, there are many molecular ways of constructing them.

Enhancement of synaptic facilitation during the progression of kindling epilepsy by amygdala stimulations

1993 ◽  
Vol 70 (2) ◽  
pp. 602-609 ◽  
Author(s):  
S. Matsuura ◽  
K. Hirayama ◽  
R. Murata
Keyword(s):  
Quantitative Analysis ◽  
Long Term Potentiation ◽  
Progressive Increase ◽  
Friedman Test ◽  
Single Test ◽  
Term Potentiation ◽  
Excitatory Component ◽  
Activity Dependent ◽  
Excitatory Potential

1. A quantitative analysis of facilitation during the kindling stimulation to the amygdala was conducted by measuring the area between the excitatory potential and the baseline in the averaged tetanic response recorded at the entorhinal cortex. The changes in facilitation were then compared with the development of electrographic afterdischarges (AD) and behavioral seizures in response to successive kindling stimulations. 2. Kindling train pulses (n = 99 or 100; duration: 0.5 ms; frequency: 10 Hz; intensity: AD threshold) were applied to conscious rats until at least one generalized seizure occurred or until 13 stimuli were delivered. 3. Facilitation of the entorhinal responses by kindling stimulation first occurred in the monosynaptic excitatory component and was then followed by a progressive increase in the polysynaptic component that was manifested as the later negative peaks. A clear progressive enhancement was observed in the facilitation by successive kindling stimulations, which also induced prolongation of the AD duration and progression of the seizure stages, indicating that activity-dependent enhancement of facilitation (EF) occurred during the progression of kindling epilepsy. 4. Quantitative analysis revealed that the EF that occurred with the progression of seizure stages was statistically significant (P < 0.001, Friedman test). The AD duration (r = 0.89) and the long-term potentiation (r = 0.85) of the entorhinal responses by single test amygdala stimuli showed a very good linear relation to the EF.(ABSTRACT TRUNCATED AT 250 WORDS)

Does endogenous zinc protoporphyrin modulate carbon monoxide formation from heme? Implications for long-term potentiation, memory, and cognitive function

1993 ◽  
Vol 71 (10-11) ◽  
pp. 753-754 ◽  
Author(s):  
Gerald S. Marks ◽  
Kanji Nakatsu ◽  
James F. Brien
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Cell Function ◽  
Physiological Role ◽  
Long Term Potentiation ◽  
Biological Properties ◽  
Zinc Protoporphyrin ◽  
Term Potentiation ◽  
Oxygenase Activity

Carbon monoxide, which is formed endogenously from heme catabolism catalyzed by heme oxygenase and shares some of the chemical and biological properties of nitric oxide, may play a similar role as a widespread signal transduction mechanism for the regulation of cell function and communication. Zinc protoporphyrin, an inhibitor of heme oxygenase, prevents induction of long-term potentiation. Zinc protoporphyrin is an endogenous substance and we suggest that it has a physiological role, by modulating heme oxygenase activity and, therefore, formation of carbon monoxide from heme. This in turn would modulate long-term potentiation, memory, and cognitive function.Key words: zinc protoporphyrin, carbon monoxide, heme oxygenase, long-term potentiation.

Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Shigetaka Yoshida
Keyword(s):  
Central Nervous System ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Synaptic Changes ◽  
Adhesive Molecules ◽  
High Level ◽  
Activity Dependent ◽  
The Brain

Abstract Klk8 is a tryptic serine protease with limited substrate specificity. Klk8 mRNA is expressed in many developing organs, whereas its expression is confined to limited regions, including the hippocampus, in adults. In the hippocampus, Klk8 is involved in activity-dependent synaptic changes such as long-term potentiation, which was found to be suppressed in Klk8 knockout (KO) mice. Oligodendrocytes only expressed Klk8 mRNA after injury to the central nervous system. The epidermis of the skin is one of the tissues that exhibits a high level of KLK8 expression. Klk8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis. Klk8 might thus be involved in tissue development and rearrangement.

scholarly journals Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

2010 ◽  
Vol 103 (1) ◽  
pp. 479-489 ◽  
Author(s):  
Hey-Kyoung Lee ◽  
Kogo Takamiya ◽  
Kaiwen He ◽  
Lihua Song ◽  
Richard L. Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Phosphorylation Sites ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Ampa Receptor Subunit ◽  
Glur1 Subunit ◽  
Activity Dependent

Activity-dependent changes in excitatory synaptic transmission in the CNS have been shown to depend on the regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). In particular, several lines of evidence suggest that reversible phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1, also referred to as GluA1 or GluR-A) plays a role in long-term potentiation (LTP) and long-term depression (LTD). We previously reported that regulation of serines (S) 831 and 845 on the GluR1 subunit may play a critical role in bidirectional synaptic plasticity in the Schaffer collateral inputs to CA1. Specifically, gene knockin mice lacking both S831 and S845 phosphorylation sites (“double phosphomutants”), where both serine residues were replaced by alanines (A), showed a faster decaying LTP and a deficit in LTD. To determine which of the two phosphorylation sites was responsible for the phenotype, we have now generated two lines of gene knockin mice: one that specifically lacks S831 (S831A mutants) and another that lacks only S845 (S845A mutants). We found that S831A mutants display normal LTP and LTD, whereas S845A mutants show a specific deficit in LTD. Taken together with our previous results from the “double phosphomutants,” our data suggest that either S831 or S845 alone may support LTP, whereas the S845 site is critical for LTD expression.

AMPA receptor phosphorylation during synaptic plasticity

2005 ◽  
Vol 33 (6) ◽  
pp. 1354-1356 ◽  
Author(s):  
J. Boehm ◽  
R. Malinow
Keyword(s):  
Protein Kinase ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Dependent Protein Kinase ◽  
Enhanced Transmission ◽  
Calcium Calmodulin Dependent ◽  
Term Potentiation ◽  
Dependent Protein ◽  
Biochemical Analyses

A widely studied example of vertebrate plasticity is LTP (long-term potentiation), the persistent synaptic enhancement that follows a brief period of coinciding pre- and post-synaptic activity. During LTP, different kinases, including CaMKII (calcium/calmodulin-dependent protein kinase II) and protein kinase A, become activated and play critical roles in induction and maintenance of enhanced transmission. Biochemical analyses have revealed several regulated phosphorylation sites in the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunits, GluR1 and GluR4. The regulated insertion of these receptors is a key event in the induction of LTP. Here, we discuss the phosphorylation of GluR1 and GluR4 and its role in receptor delivery and neuronal plasticity.

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