PMID- 21640715
OWN - NLM
STAT- MEDLINE
DCOM- 20110913
LR  - 20161125
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 82
IP  - 4
DP  - 2011 Aug 15
TI  - The cytoskeleton plays a modulatory role in the association between STIM1 and the 
      Ca2+ channel subunits Orai1 and TRPC1.
PG  - 400-10
LID - 10.1016/j.bcp.2011.05.017 [doi]
AB  - Store-operated Ca(2+) entry (SOCE) is a major pathway for Ca(2+) influx in 
      non-excitable cells. Recent studies favour a conformational coupling mechanism 
      between the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and Ca(2+) permeable 
      channels in the plasma membrane to explain SOCE. Previous studies have reported a 
      role for the cytoskeleton modulating the activation of SOCE; therefore, here we 
      have investigated whether the interaction between STIM1 and the Ca(2+) permeable 
      channels is modulated by the actin or microtubular network. In HEK-293 cells, 
      treatment with the microtubular disrupter colchicine enhanced both the activation 
      of SOCE and the association between STIM1 and Orai1 or TRPC1 induced by 
      thapsigargin (TG). Conversely, stabilization of the microtubules by paclitaxel 
      attenuated TG-evoked activation of SOCE and the interaction between STIM1 and the 
      Ca(2+) channels Orai1 and TRPC1, altogether suggesting that the microtubules act 
      as a negative regulator of SOCE. Stabilization of the cortical actin filament 
      layer results in inhibition of TG-evoked both association between STIM1, Orai1 
      and TRPC1 and SOCE. Interestingly, disruption of the actin filament network by 
      cytochalasin D did not significantly modify TG-evoked association between STIM1 
      and Orai1 or TRPC1 but enhanced TG-stimulated SOCE. Finally, inhibition of 
      calmodulin by calmidazolium enhances TG-evoked SOCE and disruption of the actin 
      cytoskeleton results in inhibition of TG-evoked association of calmodulin with 
      Orai1 and TRPC1. Thus, we demonstrate that the cytoskeleton plays an essential 
      role in the regulation of SOCE through the modulation of the interaction between 
      their main molecular components.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Galan, Carmen
AU  - Galan C
AD  - Department of Physiology (Cellular Physiology Research Group), University of 
      Extremadura, 10071 Caceres, Spain.
FAU - Dionisio, Natalia
AU  - Dionisio N
FAU - Smani, Tarik
AU  - Smani T
FAU - Salido, Gines M
AU  - Salido GM
FAU - Rosado, Juan A
AU  - Rosado JA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110527
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Calcium Channels)
RN  - 0 (Calmodulin)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (ORAI1 Protein)
RN  - 0 (ORAI1 protein, human)
RN  - 0 (Protein Subunits)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Calcium Channels/*metabolism
MH  - Calcium Signaling/drug effects/physiology
MH  - Calmodulin/antagonists & inhibitors
MH  - Cytoskeleton/drug effects/metabolism/*physiology
MH  - HEK293 Cells
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - ORAI1 Protein
MH  - Paclitaxel/pharmacology
MH  - Protein Binding/physiology
MH  - Protein Subunits/metabolism
MH  - Stromal Interaction Molecule 1
MH  - TRPC Cation Channels/*metabolism
EDAT- 2011/06/07 06:00
MHDA- 2011/09/14 06:00
CRDT- 2011/06/07 06:00
PHST- 2011/02/25 00:00 [received]
PHST- 2011/05/15 00:00 [revised]
PHST- 2011/05/18 00:00 [accepted]
PHST- 2011/06/07 06:00 [entrez]
PHST- 2011/06/07 06:00 [pubmed]
PHST- 2011/09/14 06:00 [medline]
AID - S0006-2952(11)00330-3 [pii]
AID - 10.1016/j.bcp.2011.05.017 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2011 Aug 15;82(4):400-10. doi: 10.1016/j.bcp.2011.05.017. Epub 
      2011 May 27.