Cytoskeleton in Mast Cell Signaling

Abstract

Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling.

Cinnamaldehyde derivatives inhibit degranulation and inflammatory mediator production in rat basophilic leukemia cells

“…The effects of IgE and PMA/A23187 on mast cells are known to activate PKC and extracellular Ca 2 + uptake [6,11,23,42,44,46]. These effects control degranulation, cytoskeleton rearrangement, and gene expression of pro-inflammatory cytokines in mast cells [5-8, 19,46].…”

Complex chemoattractive and chemorepellent Kit signals revealed by direct imaging of murine mast cells in microfluidic gradient chambers

“…35 PLC-gamma and PLD are prominent targets of Kit signaling, and both PKC activation and InsP3 generation are known to occur after Kit stimulation. 13,36,37 The mechanism, by which the intensity of Kit signals could cause differential levels of activation of PKC, PLC-gamma, or PLD, is not known. We have previously described topological changes in the distribution of Kit, the PI3K p85 regulatory subunit, and the phosphatase and tensin homologue (PTEN) after Kit stimulation.…”

Mast cells in airway diseases and interstitial lung disease

“…Mast cells regulate adaptive immune responses when they encounter antigen that crosslinks immunoglobulin E (IgE) bound to the high affinity IgE receptor, FcεRI (for review see (Rivera and Gilfillan, 2006)). Aggregation of FcεRI triggers a number of signalling pathways that lead to the release of Ca 2+ from intracellular stores, influx of extracellular Ca 2+ and reorganization of the cytoskeleton that are all critical processes for the release of pre-stored and newly generated mediators (Allen et al, 2009; Cruse et al, 2013; Draber et al, 2012; Gilfillan and Beaven, 2011; Gilfillan and Tkaczyk, 2006; Hajkova et al, 2011; Rivera and Gilfillan, 2006). Mast cells can also respond to a variety of alternative stimuli that may inhibit or augment FcεRI-dependent responses.…”