PMID- 34550354
OWN - NLM
STAT- MEDLINE
DCOM- 20211026
LR  - 20220531
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 134
IP  - 9
DP  - 2021 May 1
TI  - RACK1 plays a critical role in mast cell secretion and Ca2+ mobilization by 
      modulating F-actin dynamics.
LID - 10.1242/jcs.252585 [doi]
LID - jcs252585
AB  - 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 Orai1 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.
CI  - (c) 2021. Published by The Company of Biologists Ltd.
FAU - Filho, Edismauro G Freitas
AU  - Filho EGF
AUID- ORCID: 0000-0002-1910-1085
AD  - Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Av. Bandeirantes 3900, 
      Ribeirao Preto, SP 14049-900, Brazil.
FAU - da Silva, Elaine Z M
AU  - da Silva EZM
AUID- ORCID: 0000-0002-2749-6275
AD  - Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Av. Bandeirantes 3900, 
      Ribeirao Preto, SP 14049-900, Brazil.
FAU - Ong, Hwei Ling
AU  - Ong HL
AD  - Secretory Physiology Section, National Institute of Dental and Craniofacial 
      Research, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Swaim, William D
AU  - Swaim WD
AUID- ORCID: 0000-0002-2880-6378
AD  - Secretory Physiology Section, National Institute of Dental and Craniofacial 
      Research, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Ambudkar, Indu S
AU  - Ambudkar IS
AUID- ORCID: 0000-0002-9559-8679
AD  - Secretory Physiology Section, National Institute of Dental and Craniofacial 
      Research, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Oliver, Constance
AU  - Oliver C
AUID- ORCID: 0000-0002-8633-4612
AD  - Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Av. Bandeirantes 3900, 
      Ribeirao Preto, SP 14049-900, Brazil.
FAU - Jamur, Maria Celia
AU  - Jamur MC
AUID- ORCID: 0000-0001-7065-8543
AD  - Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Av. Bandeirantes 3900, 
      Ribeirao Preto, SP 14049-900, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210513
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RACK1 protein, human)
RN  - 0 (Receptors for Activated C Kinase)
RN  - 67526-95-8 (Thapsigargin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actin Cytoskeleton
MH  - *Actins/genetics
MH  - *Calcium
MH  - Humans
MH  - Mast Cells
MH  - Neoplasm Proteins/genetics
MH  - Receptors for Activated C Kinase/genetics
MH  - Thapsigargin
PMC - PMC8380048
OTO - NOTNLM
OT  - Actin cytoskeleton
OT  - Degranulation
OT  - Mast cells
OT  - RACK1
OT  - Store-operated Ca2+ entry
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2021/09/23 06:00
MHDA- 2021/10/27 06:00
PMCR- 2022/05/13
CRDT- 2021/09/22 12:24
PHST- 2020/08/04 00:00 [received]
PHST- 2021/03/15 00:00 [accepted]
PHST- 2021/09/22 12:24 [entrez]
PHST- 2021/09/23 06:00 [pubmed]
PHST- 2021/10/27 06:00 [medline]
PHST- 2022/05/13 00:00 [pmc-release]
AID - 263932 [pii]
AID - JCS252585 [pii]
AID - 10.1242/jcs.252585 [doi]
PST - ppublish
SO  - J Cell Sci. 2021 May 1;134(9):jcs252585. doi: 10.1242/jcs.252585. Epub 2021 May 
      13.