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PMID: 15998803 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane.

The Journal of cell biology ·Vol. 170 ·No. 1 ·2005-07-04 ·Pages 115-26

Nishida K, Yamasaki S, Ito Y, Kabu K, Hattori K, Tezuka T, Nishizumi H, Kitamura D, Goitsuka R, Geha RS, Yamamoto T, Yagi T, Hirano T

Abstract

The aggregation of high affinity IgE receptors (Fcepsilon receptor I [FcepsilonRI]) on mast cells is potent stimulus for the release of inflammatory and allergic mediators from cytoplasmic granules. However, the molecular mechanism of degranulation has not yet been established. It is still unclear how FcepsilonRI-mediated signal transduction ultimately regulates the reorganization of the cytoskeleton and how these events lead to degranulation. Here, we show that FcepsilonRI stimulation triggers the formation of microtubules in a manner independent of calcium. Drugs affecting microtubule dynamics effectively suppressed the FcepsilonRI-mediated translocation of granules to the plasma membrane and degranulation. Furthermore, the translocation of granules to the plasma membrane occurred in a calcium-independent manner, but the release of mediators and granule-plasma membrane fusion were completely dependent on calcium. Thus, the degranulation process can be dissected into two events: the calcium-independent microtubule-dependent translocation of granules to the plasma membrane and calcium-dependent membrane fusion and exocytosis. Finally, we show that the Fyn/Gab2/RhoA (but not Lyn/SLP-76) signaling pathway plays a critical role in the calcium-independent microtubule-dependent pathway.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Calcium/metabolism Calcium Signaling/drug effects,immunology Cell Degranulation/physiology Cell Membrane/immunology Cells, Cultured Exocytosis/drug effects,immunology Inflammation Mediators/immunology,metabolism Mast Cells/cytology,immunology,metabolism Membrane Fusion/drug effects,immunology Mice Mice, Inbred C57BL Microtubules/metabolism Phosphoproteins/metabolism Protein Transport/drug effects,immunology Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-fyn Receptor Aggregation/immunology Receptors, IgE/immunology Secretory Vesicles/immunology,metabolism Signal Transduction/drug effects,immunology rhoA GTP-Binding Protein/metabolism src-Family Kinases/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Gab2 protein, mouse Inflammation Mediators Phosphoproteins Proto-Oncogene Proteins Receptors, IgE Fyn protein, mouse Proto-Oncogene Proteins c-fyn src-Family Kinases rhoA GTP-Binding Protein Calcium
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Nishida Keigo
Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.
Yamasaki Satoru
Ito Yukitaka
Kabu Koki
Hattori Kotaro
Tezuka Tohru
Nishizumi Hirofumi
Kitamura Daisuke
Goitsuka Ryo
Geha Raif S
Yamamoto Tadashi
Yagi Takeshi
Hirano Toshio
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200501111
Published
2005-07-04
Pages
115-26
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171390
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1083/jcb.200501111 PMC Full Text View journal details
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