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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 7
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: Journal of Cell Science; v. 134, n. 9 MAY 2021.
Web of Science Citations: 1
Abstract

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. (AU)

FAPESP's process: 17/14645-4 - The involvement of RACK1 in the release of mast cell mediators.
Grantee:Maria Célia Jamur
Support type: Regular Research Grants
FAPESP's process: 09/54014-7 - Acquisition of a biophotonic imaging system and a multiphoton microscopy system for in vivo imaging
Grantee:Enilza Maria Espreafico
Support type: Multi-user Equipment Program
FAPESP's process: 17/18618-1 - Interaction between mast cells and endothelial cells during in vitro angiogenesis
Grantee:Constance Oliver
Support type: Regular Research Grants
FAPESP's process: 16/13228-8 - Genetic study of LEKTI superexpression in HNSCC mouse model
Grantee:Elaine Zayas Marcelino da Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/21988-2 - The role of the scaffold protein RACK1 in Ca2+ signaling in mast cells
Grantee:Edismauro Garcia Freitas Filho
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 15/16673-0 - The role of the scaffold protein RACK1 in mast cell activation
Grantee:Edismauro Garcia Freitas Filho
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 09/54013-0 - Functional correlation between mast cells and tumor angiogenesis
Grantee:Maria Célia Jamur
Support type: Multi-user Equipment Program