PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells
@article{Adhikari2017PKCdependentPO, title={PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells}, author={Pratikshya Adhikari and Hao Xu}, journal={Inflammation Research}, year={2017}, volume={67}, pages={1-3} }
Protein Kinase C (PKC) regulates the release of pro-inflammatory compounds from IgE/antigen-activated mast cells by unknown mechanisms. In this study, we show for the first time that PKC inhibitor Ro-03-0432, which inhibits RBL-2H3 exocytosis/degranulation in a concentration-dependent fashion, prevents the phosphorylation of membrane fusion factor Munc18a at Ser 313. Our study provides fresh evidence that PKC-dependent protein phosphorylation may contribute to the intricate regulation of mast…
12 Citations
Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle–regulated exocytosis in mast cells
- BiologyThe Journal of Biological Chemistry
- 2018
MC-regulated exocytosis is required for the anaphylactic response, and Munc 18-2 is the sole Munc18 isoform that mediates membrane fusion during MC degranulation, according to a high-resolution analysis of plasma membrane capacitance.
Imaging of RBL-2H3 Cell Degranulation by Atomic Force Microscopy
- Biology2022 IEEE International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO)
- 2022
The results showed that the effect of anti-DNP IgE on RBL-2H3 cells varied with time, peaking at 8–12 hours, and the physical changes of cell degranulation based on AFM still need to be studied.
Munc18-2, but not Munc18-1 or Munc18-3, regulates platelet exocytosis, hemostasis, and thrombosis
- Biology, MedicineThe Journal of Biological Chemistry
- 2019
Munc18-2, but not Munc18-1 or Munc 18-3, is essential for regulated exocytosis in platelets and platelet participation in thrombosis and hemostasis.
Syntaxin 3, but not syntaxin 4, is required for mast cell–regulated exocytosis, where it plays a primary role mediating compound exocytosis
- BiologyThe Journal of Biological Chemistry
- 2018
In vivo model of passive systemic anaphylaxis showed that the residual exocytic function of Stx3-deficient MCs was sufficient to drive a full anaphyactic response in mice, indicating that an Stx other than Stx 3 and -4 is also required for exocytosis in MCs.
Diverse exocytic pathways for mast cell mediators.
- BiologyBiochemical Society transactions
- 2018
This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells and discusses strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases.
Curcumin suppresses oxidative stress via regulation of ROS/NF-κB signaling pathway to protect retinal vascular endothelial cell in diabetic retinopathy
- BiologyMolecular & Cellular Toxicology
- 2021
It was found that curcumin reduced the reactive oxygen species (ROS) and relieved the apoptosis in RRVECs exposed to the high glucose by flow cytometry, and it was revealed that the increased activity of NF-κB and phosphorylated NF-β in RRvECs induced by high glucose concentration was significantly suppressed byCurcumin.
NLRP3 inflammasome contributes to neurovascular unit damage in stroke
- Medicine, BiologyJournal of drug targeting
- 2019
Evidence on this topic suggests that targeting NLRP3-mediated inflammation at multiple levels may provide a new therapeutic strategy to prevent the deterioration of neurovascular units after stroke.
De novo STXBP1 mutation in a child with developmental delay and spasticity reveals a major structural alteration in the interface with syntaxin 1A
- BiologyAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- 2020
This study provides a direct link between the outcome of a novel variant in STXBP1 and protein structure and dynamics, and the structural change upon mutation drives an alteration in synaptic function.
Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms
- Biology, MedicineActa Pharmacologica Sinica
- 2019
Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated, and the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cdoxicity.
Systematically characterize the substance basis of Jinzhen oral liquid and their pharmacological mechanism using UPLC-Q-TOF/MS combined with network pharmacology analysis
- Biology, ChemistryJournal of food and drug analysis
- 2019
References
SHOWING 1-10 OF 10 REFERENCES
Phosphorylation of SNAP-23 by IκB Kinase 2 Regulates Mast Cell Degranulation
- Biology, MedicineCell
- 2008
Phosphorylation of Munc18 by Protein Kinase C Regulates the Kinetics of Exocytosis*
- BiologyThe Journal of Biological Chemistry
- 2003
The results suggest that the dynamics of vesicle release events during exocytosis are controlled by PKC directly through phosphorylation of Munc18 on Ser-313, which may provide a mechanism for the control of exocyTosis and thereby synaptic plasticity.
Phosphorylation of Munc-18/n-Sec1/rbSec1 by Protein Kinase C
- BiologyThe Journal of Biological Chemistry
- 1996
It is shown that recombinant Munc-18 is phosphorylated by conventional PKC in a Ca- and phospholipid-dependent manner in a cell-free system and this results suggest that the PKC-catalyzed phosphorylation of Munm-18 plays an important role in regulating the interaction of MunC-18 with syntaxin and thereby the docking and/or the fusion of synaptic vesicles with the presynaptic plasma membrane.
Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation.
- Biology, MedicineThe Journal of pharmacology and experimental therapeutics
- 1994
Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses and demonstrating the crucial role for PKC in T-cell activation and that selective p.o.C inhibitors are efficacious in preventing T- cell driven chronic inflammatory responses in vivo.
The SNARE Machinery in Mast Cell Secretion
- BiologyFront. Immun.
- 2012
This review summarizes the current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion and identifies several accessory regulators involved in membrane fusion events during exocytosis.
Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation
- BiologyProceedings of the National Academy of Sciences
- 2013
The results demonstrate the crucial roles of the hydrophobic pocket of Munc18 in mast cell degranulation, which include the regulation of syntaxin-11, and suggest that the functional importance of this region is significantly different between neuronal and immune cell exocytosis.
An Extended Helical Conformation in Domain 3a of Munc18-1 Provides a Template for SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Complex Assembly*
- BiologyThe Journal of Biological Chemistry
- 2014
The data suggest that helix 12 provides a folding template for VAMP2, accelerating SNAREpin assembly and membrane fusion, and analogous SEC1/Munc18-SNARE interactions at other transport steps may provide a general mechanism to drive lipid bilayer merger.
Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation
- BiologyProceedings of the National Academy of Sciences
- 2010
The results suggest the possibility that structural transitions occur in both Munc18-1 and Syntaxin1 during their binary interaction, and hypothesize that Munc 18-1 domain 3a undergoes a conformational change that may allow coiled-coil interactions with SNARE complexes.
Differential Effects of Munc18s on Multiple Degranulation-Relevant Trans-SNARE Complexes
- BiologyPloS one
- 2015
It is shown for the first time that Munc18a operates synergistically with SNAP-23-based non-neuronal SNARE complexes (i to iv) in lipid mixing, in contrast to Munc 18b and c, which exhibit no positive effect on any SNARE combination tested.
Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release
- BiologyeLife
- 2014
It is found that two PKC phosphorylation sites of Munc18-1 are critically important for PTP, which identifies the presynaptic target protein for the action of PKC during PTP.