PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells

  title={PKC-dependent phosphorylation of Munc18a at Ser313 in activated RBL-2H3 cells},
  author={Pratikshya Adhikari and Hao Xu},
  journal={Inflammation Research},
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… 

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Phosphorylation of Munc18 by Protein Kinase C Regulates the Kinetics of Exocytosis*

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

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.

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

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

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*

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

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

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

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