PMID- 22842488
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20161125
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 84
IP  - 8
DP  - 2012 Oct 15
TI  - Store-independent pathways for cytosolic STIM1 clustering in the regulation of 
      store-operated Ca(2+) influx.
PG  - 1024-35
LID - S0006-2952(12)00495-9 [pii]
LID - 10.1016/j.bcp.2012.07.013 [doi]
AB  - STIM1 is a Ca(2+) sensing molecule. Once the Ca(2+) stores are depleted, STIM1 
      moves towards the plasma membrane (PM) (translocation), forms puncta 
      (clustering), and triggers store-operated Ca(2+) entry (SOCE). Although this 
      process has been regarded as a main mechanism for store-operated Ca(2+) channel 
      activation, the STIM1 clustering is still unclear. Here we discovered a new 
      phenomenon of STIM1 clustering, which is not triggered by endoplasmic reticulum 
      (ER) Ca(2+) depletion. STIM1 subplasmalemmal translocation and clustering can be 
      induced by ER Ca(2+) store depletion with thapsigargin (TG), G-protein-coupled 
      receptor activator trypsin and ryanodine receptor (RyR) agonists caffeine and 
      4-chloro-3-ethylphenol (4-CEP) in the HEK293 cells stably transfected with 
      STIM1-EYFP. The STIM1 clustering induced by TG was more sustained than that 
      induced by trypsin and RyR agonists. Interestingly, 4-CEP-induced STIM1 
      clustering also happened in the cytosol without ER Ca(2+) store depletion. 
      Application of some pharmacological regulators including flufenamic acid, 2-APB, 
      and carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) at concentrations 
      without affecting ER Ca(2+) store also evoked cytosolic STIM1 clustering. 
      However, the direct store-operated ORAI channel blockers (SKF-96365, Gd(3+) and 
      diethylstilbestrol) or the signaling pathway inhibitors (genistein, wortmannin, 
      Y-27632, forskolin and GF109203X) did not change the STIM1 movement. Disruption 
      of cytoskeleton by colchicine and cytochalasin D also showed no effect on STIM1 
      movement. We concluded that STIM1 clustering and translocation are two dynamic 
      processes that can be pharmacologically dissociated. The ER Ca(2+) 
      store-independent mechanism for STIM1 clustering is a new alternative mechanism 
      for regulating store-operated channel activity, which could act as a new 
      pharmacological target.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Zeng, Bo
AU  - Zeng B
AD  - Centre for Cardiovascular and Metabolic Research, Hull York Medical School, 
      University of Hull, Hull, HU6 7RX, UK.
FAU - Chen, Gui-Lan
AU  - Chen GL
FAU - Xu, Shang-Zhong
AU  - Xu SZ
LA  - eng
GR  - PG/08/071/25473/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120726
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 15662-33-6 (Ryanodine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*metabolism
MH  - Cytosol/*drug effects/metabolism
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Ion Transport
MH  - Membrane Proteins/*metabolism
MH  - Mitochondria/metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Ryanodine/metabolism
MH  - Ryanodine Receptor Calcium Release Channel/drug effects
MH  - Stromal Interaction Molecule 1
EDAT- 2012/07/31 06:00
MHDA- 2012/12/14 06:00
CRDT- 2012/07/31 06:00
PHST- 2012/05/30 00:00 [received]
PHST- 2012/07/08 00:00 [revised]
PHST- 2012/07/16 00:00 [accepted]
PHST- 2012/07/31 06:00 [entrez]
PHST- 2012/07/31 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
AID - S0006-2952(12)00495-9 [pii]
AID - 10.1016/j.bcp.2012.07.013 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2012 Oct 15;84(8):1024-35. doi: 10.1016/j.bcp.2012.07.013. 
      Epub 2012 Jul 26.