PMID- 23077736
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20181023
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1823
IP  - 10
DP  - 2012 Oct
TI  - Two-pore channel 2 (TPC2) modulates store-operated Ca(2+) entry.
PG  - 1976-83
LID - 10.1016/j.bbamcr.2012.08.002 [doi]
AB  - Two-pore channels (TCPS) are NAADP-sensitive receptor channels that conduct 
      Ca(2+) efflux from the intracellular stores. Discharge of the internal Ca(2+) 
      pools results in the activation of store-operated Ca(2+) entry (SOCE); however, 
      the role of TPCs in the modulation of SOCE remains unexplored. Mammalian cells 
      express three TPCs: TPC1, TPC2 and TPC3, a pseudogene in humans. Here we report 
      that MEG01 and HEK293 cells endogenously express TPC1 and TPC2. Silencing TPC2 
      expression results in attenuation of the rate and extent of thapsigargin 
      (TG)-evoked SOCE both in MEG01 and HEK293 cells, without having any effect on the 
      ability of cells to accumulate Ca(2+) into the TG-sensitive stores. Similarly, 
      silencing of native TPC2 expression reduced thrombin-induced Ca(2+) entry both in 
      MEG01 and HEK293 cells. Biotinylation analysis revealed that TPC1 and TPC2 are 
      expressed in internal membranes. Finally, co-immunoprecipitation experiments 
      indicated that endogenously expressed TPC2, but not TPC1, assoicates STIM1 and 
      Orai1, but not with TRPC1, in MEG01 cells with depleted intracellular Ca(2+) 
      stores, but not in resting cells. These results provide strong evidence for 
      modulation of SOCE by TPC2 involving de novo association between TPC2 and STIM1, 
      as well as Orai1, in human cells.
FAU - Lopez, Jose
AU  - Lopez J
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, Caceres, Spain.
FAU - Dionisio, Natalia
AU  - Dionisio N
FAU - Berna-Erro, Alejandro
AU  - Berna-Erro A
FAU - Galan, Carmen
AU  - Galan C
FAU - Salido, Gines M
AU  - Salido GM
FAU - Rosado, Juan A
AU  - Rosado JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Calcium Channels)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (ORAI1 Protein)
RN  - 0 (ORAI1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 0 (TPCN1 protein, human)
RN  - 0 (TPCN2 protein, human)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*metabolism
MH  - Calcium Channels/genetics/*metabolism
MH  - Cell Membrane/drug effects/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Gene Silencing/drug effects
MH  - HEK293 Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Membrane Proteins/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - ORAI1 Protein
MH  - RNA, Messenger/genetics/metabolism
MH  - Stromal Interaction Molecule 1
MH  - Thapsigargin/pharmacology
MH  - Thrombin/pharmacology
EDAT- 2012/10/19 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/10/19 06:00
PHST- 2012/10/19 06:00 [entrez]
PHST- 2012/10/19 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - S0167-4889(12)00226-1 [pii]
AID - 10.1016/j.bbamcr.2012.08.002 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2012 Oct;1823(10):1976-83. doi: 
      10.1016/j.bbamcr.2012.08.002.