RACK1 plays a critical role in mast cell secretion and Ca2+ mobilization by modulating F-actin dynamics

被引:8
作者
Freitas Filho, Edismauro G. [1 ]
da Silva, Elaine Z. M. [1 ]
Ong, Hwei Ling [2 ]
Swaim, William D. [2 ]
Ambudkar, Indu S. [2 ]
Oliver, Constance [1 ]
Jamur, Maria Celia [1 ]
机构
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, Av Bandeiranles 3900, BR-14049900 Ribeirao Preto, SP, Brazil
[2] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA
基金
巴西圣保罗研究基金会;
关键词
RACK1; Degranulation; Actin cytoskeleton; Store-operated Ca2+ entry; Mast cells; PROTEIN-KINASE-C; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; CARBOXYL-TERMINUS; IN-VITRO; ACTIVATION; DEGRANULATION; RELEASE; BINDING; CYTOSKELETON;
D O I
10.1242/jcs.252585
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Although RACK1 is known to act as a signaling hub in immune cells, its presence and role in mast cells (MCs) is undetermined. MC activation via antigen stimulation results in mediator release and is preceded by cytoskeleton reorganization and Ca2+ mobilization. In this study, we found that RACK1 was distributed throughout the MC cytoplasm both in vivo and in vitro. After RACK1 knockdown (KD), MCs were rounded, and the cortical F-actin was fragmented. Following antigen stimulation, in RACK1 KD MCs, there was a reduction in cortical F-actin, an increase in monomeric G-actin and a failure to organize F-actin. RACK1 KD also increased and accelerated degranulation. CD63(+) secretory granules were localized in F-actin-free cortical regions in non-stimulated RACK1 KD MCs. Additionally, RACK1 KD increased antigen-stimulated Ca2+ mobilization, but attenuated antigen-stimulated depletion of ER Ca2+ stores and thapsigargin-induced Ca2+ entry. Following MC activation there was also an increase in interaction of RACK1 with Orail Ca2+-channels, beta-actin and the actin-binding proteins vinculin and MyoVa. These results show that RACK1 is a critical regulator of actin dynamics, affecting mediator secretion and Ca2+ signaling in MCs. This article has an associated First Person interview with the first author of the paper.
引用
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页数:19
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