scholarly journals Long-Term Potentiation of Exocytosis and Cell Membrane Repair in Fibroblasts

2003 ◽  
Vol 14 (1) ◽  
pp. 93-106 ◽  
Author(s):  
Tatsuru Togo ◽  
Janet M. Alderton ◽  
Richard A. Steinhardt
Keyword(s):  
Long Term Potentiation ◽  
Camp Response Element Binding ◽  
Membrane Repair ◽  
Regulated Exocytosis ◽  
3T3 Fibroblasts ◽  
Term Potentiation ◽  
Element Binding Protein ◽  
Dependent Protein ◽  
Membrane Resealing

We previously found that a microdisruption of the plasma membrane evokes Ca2+-regulated exocytosis near the wound site, which is essential for membrane resealing. We demonstrate herein that repeated membrane disruption reveals long-term potentiation of Ca2+-regulated exocytosis in 3T3 fibroblasts, which is closely correlated with faster membrane resealing rates. This potentiation of exocytosis is cAMP-dependent protein kinase A dependent in the early stages (minutes), in the intermediate term (hours) requires protein synthesis, and for long term (24 h) depends on the activation of cAMP response element-binding protein (CREB). We were able to demonstrate that wounding cells activated CREB within 3.5 h. In all three phases, the increase in the amount of exocytosis was correlated with an increase in the rate of membrane resealing. However, a brief treatment with forskolin, which is effective for short-term potentiation and which could also activate CREB, was not sufficient to induce long-term potentiation of resealing. These results imply that long-term potentiation by CREB required activation by another, cAMP-independent pathway.

scholarly journals Inducible molecular switches for the study of long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 797-804 ◽  
Author(s):  
Gaël Hédou ◽  
Isabelle M. Mansuy
Keyword(s):  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Knock Out ◽  
Technical Developments ◽  
Term Potentiation ◽  
Dependent Protein ◽  
Strength And Plasticity ◽  
Regulated Gene Expression ◽  
Molecular Bases

This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene ‘knock-out’ technology was initially exploited to disrupt the Ca 2+ /calmodulin-dependent protein kinase II α (CaMKII α ) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKII α and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

scholarly journals Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Han-Fang Wu ◽  
Yi-Ju Chen ◽  
Su-Zhen Wu ◽  
Chi-Wei Lee ◽  
I-Tuan Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epoxide Hydrolase ◽  
Long Term Potentiation ◽  
Soluble Epoxide Hydrolase ◽  
Synaptic Function ◽  
Receptor Subunit ◽  
Dependent Protein Kinase ◽  
Term Potentiation ◽  
Dependent Protein

Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-aspartate (NMDA) receptor subunit NR2B antagonist. TPPU- or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin- (CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR- and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus.

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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