PMID- 28179072
OWN - NLM
STAT- MEDLINE
DCOM- 20180307
LR  - 20180515
IS  - 1532-1991 (Electronic)
IS  - 0143-4160 (Linking)
VI  - 65
DP  - 2017 Jul
TI  - Orai3 channel is the 2-APB-induced endoplasmic reticulum calcium leak.
PG  - 91-101
LID - S0143-4160(16)30137-3 [pii]
LID - 10.1016/j.ceca.2017.01.012 [doi]
AB  - We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca(2+) 
      leak using synthetic Ca(2+) indicators that report changes in both the 
      cytoplasmic ([Ca(2+)](i)) and the luminal ER ([Ca(2+)](ER)) Ca(2+) 
      concentrations. We have tested the hypothesis that Orai channels participate in 
      the 2-APB-induced ER Ca(2+) leak that was characterized in the companion paper. 
      The expression of the dominant negative Orai1 E106A mutant, which has been 
      reported to block the activity of all three types of Orai channels, inhibited the 
      effect of 2-APB on the [Ca(2+)](ER) but did not decrease the ER Ca(2+) leak after 
      thapsigargin (TG). Orai3 channel, but neither Orai1 nor Orai2, colocalizes with 
      expressed IP(3)R and only Orai3 channel supported the 2-APB-induced ER Ca(2+) 
      leak, while Orai1 and Orai2 inhibited this type of ER Ca(2+) leak. Decreasing the 
      expression of Orai3 inhibited the 2-APB-induced ER Ca(2+) leak but did not modify 
      the ER Ca(2+) leak revealed by inhibition of SERCA pumps with TG. However, 
      reducing the expression of Orai3 channel resulted in larger [Ca(2+)](i) response 
      after TG but only when the ER store had been overloaded with Ca(2+) by 
      eliminating the acidic internal Ca(2+) store with bafilomycin. These data suggest 
      that Orai3 channel does not participate in the TG-revealed ER Ca(2+) leak but 
      forms an ER Ca(2+) leak channel that is limiting the overloading with Ca(2+) of 
      the ER store.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Leon-Aparicio, Daniel
AU  - Leon-Aparicio D
AD  - Department of Biochemistry, Cinvestav, Mexico City, 07000, Mexico.
FAU - Pacheco, Jonathan
AU  - Pacheco J
AD  - Department of Cell Biology and Development, Instituto de Fisiologia Celular, 
      UNAM, Mexico City, 04510, Mexico.
FAU - Chavez-Reyes, Jesus
AU  - Chavez-Reyes J
AD  - Department of Biochemistry, Cinvestav, Mexico City, 07000, Mexico.
FAU - Galindo, Jose M
AU  - Galindo JM
AD  - Department of Biochemistry, Cinvestav, Mexico City, 07000, Mexico.
FAU - Valdes, Jesus
AU  - Valdes J
AD  - Department of Biochemistry, Cinvestav, Mexico City, 07000, Mexico.
FAU - Vaca, Luis
AU  - Vaca L
AD  - Department of Cell Biology and Development, Instituto de Fisiologia Celular, 
      UNAM, Mexico City, 04510, Mexico.
FAU - Guerrero-Hernandez, Agustin
AU  - Guerrero-Hernandez A
AD  - Department of Cell Biology and Development, Instituto de Fisiologia Celular, 
      UNAM, Mexico City, 04510, Mexico. Electronic address: aguerrero@cinvestav.mx.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170123
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Boron Compounds)
RN  - 0 (Calcium Channels)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Orai3 protein, human)
RN  - 67526-95-8 (Thapsigargin)
RN  - E4ES684O93 (2-aminoethoxydiphenyl borate)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Boron Compounds/*pharmacology
MH  - Calcium/*metabolism
MH  - Calcium Channels/*metabolism
MH  - Calcium Signaling/*drug effects
MH  - Endoplasmic Reticulum/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Inositol 1,4,5-Trisphosphate Receptors/metabolism
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
MH  - Thapsigargin/pharmacology
OTO - NOTNLM
OT  - 2-APB
OT  - Endoplasmic reticulum calcium leak
OT  - Luminal calcium concentration
OT  - Orai3 channel
OT  - SERCA pump
EDAT- 2017/02/10 06:00
MHDA- 2018/03/08 06:00
CRDT- 2017/02/10 06:00
PHST- 2016/08/11 00:00 [received]
PHST- 2017/01/17 00:00 [revised]
PHST- 2017/01/20 00:00 [accepted]
PHST- 2017/02/10 06:00 [pubmed]
PHST- 2018/03/08 06:00 [medline]
PHST- 2017/02/10 06:00 [entrez]
AID - S0143-4160(16)30137-3 [pii]
AID - 10.1016/j.ceca.2017.01.012 [doi]
PST - ppublish
SO  - Cell Calcium. 2017 Jul;65:91-101. doi: 10.1016/j.ceca.2017.01.012. Epub 2017 Jan 
      23.