Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2011-8-30
pubmed:abstractText
Mast cell (MC) activation via aggregation of the high affinity IgE receptor (Fc?RI) causes degranulation and release of proinflammatory mediators in a process that involves the reorganization of the actin cytoskeleton. However, the regulatory pathways and the molecular links between cytoskeletal changes and MC function are incompletely understood. In this study, we provide genetic evidence for a critical role of the actin-regulatory proteins Coronin1a (Coro1a) and Coro1b on exocytic pathways in MCs: Coro1a(-/-) bone marrow-derived MCs exhibit increased Fc?RI-mediated degranulation of secretory lysosomes but significantly reduced secretion of cytokines. Hyperdegranulation of Coro1a(-/-) MCs is further augmented by the additional loss of Coro1b. In vivo, Coro1a(-/-)Coro1b(-/-) mice displayed enhanced passive cutaneous anaphylaxis. Functional reconstitution assays revealed that the inhibitory effect of Coro1a on MC degranulation strictly correlates with cortical localization of Coro1a, requires its filamentous actin-binding activity, and is regulated by phosphorylation of Ser2 of Coro1a. Thus, coronin proteins, and in turn the actin cytoskeleton, exhibit a functional dichotomy as differential regulators of degranulation versus cytokine secretion in MC biology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1540-9538
pubmed:author
pubmed:copyrightInfo
© 2011 Föger et al.
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
208
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1777-87
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b.
pubmed:affiliation
Department of Immunology and Cell Biology, Research Center Borstel, 23845 Borstel, Germany. nfoeger@fz-borstel.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't