Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b

Föger, Niko; Jenckel, André; Orinska, Zane; Lee, Kyeong Hee; Chan, Andrew C.; Bulfone–Paus∥, Silvia

doi:10.1084/jem.20101757

Cited by 58 publications

(56 citation statements)

References 33 publications

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“…These results, together with the observation of a localized clearance of actin cytoskeleton at the degranulatory synapse, provide a mechanistic link between localized signalling and polarized secretion. Accordingly, actin cytoskeleton disassembly was previously reported in rodent mast cells stimulated with soluble antigens 41,44 . This process was proposed to allow mast cell granules to cross the cortical actin ring and reach plasma membrane 45 .…”

Section: Discussionmentioning

confidence: 74%

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

et al. 2015

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Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy. Here we show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism, which we name the antibody-dependent degranulatory synapse (ADDS), is triggered by both IgE-and IgG-targeted cells. ADDSs take place within an area of cortical actin cytoskeleton clearance in the absence of microtubule organizing centre and Golgi apparatus repositioning towards the stimulating cell. Remarkably, IgG-mediated degranulatory synapses also occur upon contact with opsonized Toxoplasma gondii tachyzoites resulting in tryptase-dependent parasite death. Our results broaden current views of mast cell degranulation by revealing that human mast cells form degranulatory synapses with antibody-targeted cells and pathogens for dedicated secretion and defence.

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Section: Discussionmentioning

confidence: 74%

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

et al. 2015

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“…that had been found to not be sensitized to food ( Figure 2C). The appearance of lysosomal-associated membrane protein 1 (LAMP-1) at the cell surface of mast cells is an established surrogate marker for antigen/IgE-mediated histamine release (28,29), and we found that WT mast cells loaded with serum from food-sensitized Was -/-mice degranulated in response to stimulation with an antigen extract from conventional chow, but not in response to an extract from a protein-free, amino acid-based elemental diet ( Figure 2C). In contrast, mast cells loaded with serum from nonfood-sensitized animals were not activated by either food extract, which further demonstrated that IgE-dependent degranulation was antigen specific and established that screening of antibody IgG1 was observed (Supplemental Figure 1D).…”

Section: Sensitization To Food Antigens and Food Allergy Are Enrichedmentioning

confidence: 99%

FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy

Lexmond¹,

Goettel²,

Lyons³

et al. 2016

Journal of Clinical Investigation

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“…Exocytosis involves the continuous reorganization of the actin cytoskeleton (13,45), and the function of many Rabs is linked with actin rearrangements (19). Therefore, to explore the potential role of the actin skeleton in mediating Rab regulatory functions on exocytosis, we repeated our screen in the presence of cytochalasin D that disrupts the actin cytoskeleton by inhibiting actin polymerization.…”

Section: The Role Of Actin In Mediating Rab Network Regulatory Functmentioning

confidence: 99%

Decoding the Regulation of Mast Cell Exocytosis by Networks of Rab GTPases

Azouz

Matsui

Fukuda

et al. 2012

The Journal of Immunology

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Exocytosis is a key event in mast cell functions. By this process, mast cells release inflammatory mediators, contained in secretory granules (SGs), which play important roles in immunity and wound healing but also provoke allergic and inflammatory responses. The mechanisms underlying mast cell exocytosis remained poorly understood. An essential step toward deciphering the mechanisms behind exocytosis is the identification of the cellular components that regulate this process. Because Rab GTPases regulate specific trafficking pathways, we screened 44 Rabs for their functional impacts on exocytosis triggered by the FcεRI or combination of Ca2+ ionophore and phorbol ester. Because exocytosis involves the continuous reorganization of the actin cytoskeleton, we also repeated our screen in the presence of cytochalasin D that inhibits actin polymerization. In this paper, we report on the identification of 30 Rabs as regulators of mast cell exocytosis, the involvement of 26 of which has heretofore not been recognized. Unexpectedly, these Rabs regulated exocytosis in a stimulus-dependent fashion, unless the actin skeleton was disrupted. Functional clustering of the identified Rabs suggested their classification as Rabs involved in SGs biogenesis or Rabs that control late steps of exocytosis. The latter could be further divided into Rabs that localize to the SGs and Rabs that regulate transport from the endocytic recycling compartment. Taken together, these findings unveil the Rab networks that control mast cell exocytosis and provide novel insights into their mechanisms of action.

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Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b

Abstract: Coronin1a inhibits mast cell degranulation through actin cytoskeletal dynamics while augmenting cytokine secretion, an effect exacerbated by additional loss of Coronin1b.

Cited by 58 publications

References 33 publications

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy

Decoding the Regulation of Mast Cell Exocytosis by Networks of Rab GTPases

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