SNAREs and associated regulators in the control of exocytosis in the RBL-2H3 mast cell line.
Mast cells participate in inflammation and allergies by releasing biologically active mediators stored in numerous cytoplasmic granules. Degranulation is tightly controlled and requires activation of cell surface receptors, such as the high affinity IgE receptor (FcepsilonRI). Here, we discuss some of the key components of the molecular machinery that regulates the final steps of fusion between the granular and plasma membrane based on results obtained with the rat mast cell line RBL-2H3. We emphasize the role of soluble N-ethylmaleimide attachment protein receptors (SNAREs) proteins such as syntaxin 4 that can promote membrane fusion through formation of a stable complex with SNAP-23. We also highlight the role of a Ser/Thr kinase found to be associated with Rab3D, a negative regulator of degranulation. Associated kinase activity, which diminishes after stimulation as a consequence of intracellular calcium increases, specifically phosphorylates syntaxin 4 thereby affecting its capacity to bind to its t-SNARE partner SNAP-23. Our results suggest a new way of how Rab3 GTPases may intersect with the function of SNAREs thought to be universal mediators of membrane fusion.
Blank
Ulrich
U
Institut Pasteur, Unité d'Immuno-Allergie, 25 rue du Dr. Roux, 75724 Cedex 15, Paris, France. ublank@pasteur.fr
Cyprien
Bettyna
B
Martin-Verdeaux
Sophie
S
Paumet
Fabienne
F
Pombo
Isabel
I
Rivera
Juan
J
Roa
Michèle
M
Varin-Blank
Nadine
N
D000818:Animals; D015550:Cell Degranulation; D008407:Mast Cells / Q000276:immunology*; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D050765:Qa-SNARE Proteins; D051381:Rats; D050600:SNARE Proteins; D014407:Tumor Cells, Cultured; D033921:Vesicular Transport Proteins; D020692:rab3 GTP-Binding Proteins / Q000502:physiology
D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C442223:Rak3D protein, rat; D017346:Protein Serine-Threonine Kinases; C492133:Rab3d protein, rat; D020692:rab3 GTP-Binding Proteins