PMID- 37332264
OWN - NLM
STAT- MEDLINE
DCOM- 20230925
LR  - 20230925
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 238
IP  - 9
DP  - 2023 Sep
TI  - Functional differences in agonist-induced plasma membrane expression of Orai1alpha 
      and Orai1beta.
PG  - 2050-2062
LID - 10.1002/jcp.31055 [doi]
AB  - Orai1 is the pore-forming subunit of the store-operated Ca(2+) release-activated 
      Ca(2+) (CRAC) channels involved in a variety of cellular functions. Two Orai1 
      variants have been identified, the long form, Orai1alpha, containing 301 amino acids, 
      and the short form, Orai1beta, which arises from alternative translation initiation 
      from methionines 64 or 71, in Orai1alpha. Orai1 is mostly expressed in the plasma 
      membrane, but a subset of Orai1 is located in intracellular compartments. Here we 
      show that Ca(2+) store depletion leads to trafficking and insertion of 
      compartmentalized Orai1alpha in the plasma membrane via a mechanism that is 
      independent on changes in cytosolic free-Ca(2+) concentration, as demonstrated by 
      cell loading with the fast intracellular Ca(2+) chelator dimethyl BAPTA in the 
      absence of extracellular Ca(2+) . Interestingly, thapsigargin (TG) was found to 
      be unable to induce translocation of Orai1beta to the plasma membrane when expressed 
      individually; by contrast, when Orai1beta is co-expressed with Orai1alpha, cell 
      treatment with TG induced rapid trafficking and insertion of compartmentalized 
      Orai1beta in the plasma membrane. Translocation of Orai1 forms to the plasma 
      membrane was found to require the integrity of the actin cytoskeleton. Finally, 
      expression of a dominant negative mutant of the small GTPase ARF6, and ARF6-T27N, 
      abolished the translocation of compartmentalized Orai1 variants to the plasma 
      membrane upon store depletion. These findings provide new insights into the 
      mechanism that regulate the plasma membrane abundance of Orai1 variants after 
      Ca(2+) store depletion.
CI  - (c) 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals 
      LLC.
FAU - Jardin, Isaac
AU  - Jardin I
AUID- ORCID: 0000-0003-4575-8264
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
FAU - Alvarado, Sandra
AU  - Alvarado S
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
FAU - Sanchez-Collado, Jose
AU  - Sanchez-Collado J
AUID- ORCID: 0000-0001-7602-9975
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
FAU - Nieto-Felipe, Joel
AU  - Nieto-Felipe J
AUID- ORCID: 0000-0001-6342-3893
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
FAU - Lopez, Jose J
AU  - Lopez JJ
AUID- ORCID: 0000-0002-5234-1478
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
FAU - Salido, Gines M
AU  - Salido GM
AUID- ORCID: 0000-0002-8687-2445
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
FAU - Rosado, Juan A
AU  - Rosado JA
AUID- ORCID: 0000-0002-9749-2325
AD  - Department of Physiology (Cellular Physiology Research Group), Institute of 
      Molecular Pathology Biomarkers (IMPB), University of Extremadura, Caceres, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230618
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Calcium Channels)
RN  - 0 (Calcium Release Activated Calcium Channels)
RN  - 0 (ORAI1 Protein)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Calcium/metabolism
MH  - *Calcium Channels/genetics/metabolism
MH  - *Calcium Release Activated Calcium Channels/metabolism
MH  - Calcium Signaling
MH  - Cell Membrane/metabolism
MH  - *ORAI1 Protein/antagonists & inhibitors/genetics/metabolism
MH  - Stromal Interaction Molecule 1/metabolism
MH  - Thapsigargin/pharmacology
MH  - Humans
MH  - HEK293 Cells
OTO - NOTNLM
OT  - ARF6
OT  - Orai1alpha
OT  - Orai1beta
OT  - actin cytoskeleton
OT  - plasma membrane
OT  - store-operated Ca2+ entry
EDAT- 2023/06/19 06:42
MHDA- 2023/09/20 06:42
CRDT- 2023/06/19 02:33
PHST- 2023/04/20 00:00 [revised]
PHST- 2023/02/08 00:00 [received]
PHST- 2023/05/24 00:00 [accepted]
PHST- 2023/09/20 06:42 [medline]
PHST- 2023/06/19 06:42 [pubmed]
PHST- 2023/06/19 02:33 [entrez]
AID - 10.1002/jcp.31055 [doi]
PST - ppublish
SO  - J Cell Physiol. 2023 Sep;238(9):2050-2062. doi: 10.1002/jcp.31055. Epub 2023 Jun 
      18.