Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity.

Behavioural time scale plasticity (BTSP) is non-Hebbian plasticity induced by integrating presynaptic and postsynaptic components separated by a behaviourally relevant time scale (seconds). BTSP in hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms that enable synapse-specific plasticity on a behavioural time scale are unknown.

Calcium transients trigger switch-like discharge of prostaglandin E in an extracellular signal-regulated kinase-dependent manner.

Prostaglandin E (PGE) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin-Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE-mediated radial spread of PKA activation (RSPA) in neighboring cells.

Visual quantification of prostaglandin E discharge from a single cell.

Calcium transients drive cells to discharge prostaglandin E (PGE). We visualized PGE-induced protein kinase A (PKA) activation and quantitated PGE secreted from a single cell by combining fluorescence microscopy and a simulation model. For this purpose, we first prepared PGE-producer cells that express either an optogenetic or a chemogenetic calcium channel stimulator: OptoSTIM1 or Gq-DREADD, respectively.

Dendritic, delayed, and stochastic CaMKII activation underlies behavioral time scale plasticity in CA1 synapses.

Behavioral time scale plasticity (BTSP), is a form of non-Hebbian plasticity induced by integrating pre- and postsynaptic components separated by behavioral time scale (seconds). BTSP in the hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms underlying this behavioral time scale (eligibility trace) and synapse specificity are unknown.

Intravital Imaging Identifies the VEGF-TXA Axis as a Critical Promoter of PGE Secretion from Tumor Cells and Immune Evasion.

Prostaglandin E (PGE) promotes tumor progression through evasion of antitumor immunity. In stark contrast to cyclooxygenase-dependent production of PGE, little is known whether PGE secretion is regulated within tumor tissues. Here, we show that VEGF-dependent release of thromboxane A (TXA) triggers Ca transients in tumor cells, culminating in PGE secretion and subsequent immune evasion in the early stages of tumorigenesis.

Single-Cell Activation of the cAMP-Signaling Pathway in 3D Tissues with FRET-Assisted Two-Photon Activation of bPAC.

Bacterial photoactivated adenylyl cyclase (bPAC) has been widely used in signal transduction research. However, due to its low two-photon absorption, bPAC cannot be efficiently activated by two-photon (2P) excitation. Taking advantage of the high two-photon absorption of monomeric teal fluorescent protein 1 (mTFP1), we herein developed 2P-activatable bPAC (2pabPAC), a fusion protein consisting of bPAC and mTFP1.

Booster, a Red-Shifted Genetically Encoded Förster Resonance Energy Transfer (FRET) Biosensor Compatible with Cyan Fluorescent Protein/Yellow Fluorescent Protein-Based FRET Biosensors and Blue Light-Responsive Optogenetic Tools.

Genetically encoded Förster resonance energy transfer (FRET)-based biosensors have been developed for the visualization of signaling molecule activities. Currently, most of them are comprised of cyan and yellow fluorescent proteins (CFP and YFP), precluding the use of multiple FRET biosensors within a single cell. Moreover, the FRET biosensors based on CFP and YFP are incompatible with the optogenetic tools that operate at blue light.

Cell adhesion signals regulate the nuclear receptor activity.

Cell adhesion is essential for proper tissue architecture and function in multicellular organisms. Cell adhesion molecules not only maintain tissue integrity but also possess signaling properties that contribute to diverse cellular events such as cell growth, survival, differentiation, polarity, and migration; however, the underlying molecular basis remains poorly defined. Here we identify that the cell adhesion signal initiated by the tight-junction protein claudin-6 (CLDN6) regulates nuclear receptor activity.

A novel occludin-targeting monoclonal antibody prevents hepatitis C virus infection .

Since hepatitis C virus (HCV) is thought to enter into host hepatocytes using the same cellular pathways regardless of the genotypes, the host factors are promising targets to prevent and treat HCV infection. Human occludin (hOCLN) is one representative entry factor, and its second extracellular loop (EC2) contributes to the species selectivity of HCV-susceptibility. However, the exact function of hOCLN during HCV entry remains unknown, and no hOCLN-targeting antibodies or synthetic drugs that prevent and treat HCV infection have yet been developed.