PMID- 18191041
OWN - NLM
STAT- MEDLINE
DCOM- 20080731
LR  - 20191210
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1783
IP  - 6
DP  - 2008 Jun
TI  - Intracellular Ca2+ store depletion induces the formation of macromolecular 
      complexes involving hTRPC1, hTRPC6, the type II IP3 receptor and SERCA3 in human 
      platelets.
PG  - 1163-76
LID - 10.1016/j.bbamcr.2007.12.008 [doi]
AB  - Endogenously expressed human canonical transient receptor potential 1 (hTRPC1) 
      and human canonical transient receptor potential 6 (hTRPC6) have been shown to 
      play a role in store-operated Ca2+ entry (SOCE) in human platelets, where two 
      mechanisms for SOCE, regulated by the dense tubular system (DTS) or the acidic 
      granules, have been identified. In cells preincubated for 1 min with 100 microM 
      flufenamic acid we show that hTRPC6 is involved in SOCE activated by both 
      mechanisms, as demonstrated by selective depletion of the DTS or the acidic 
      stores, using thapsigargin (TG) (10 nM) or 2,5-di-(tert-butyl)-1,4-hydroquinone 
      (TBHQ) (20 microM), respectively, although it is more relevant after acidic store 
      depletion. Co-immunoprecipitation experiments indicated that depletion of both 
      stores separately results in time-dependent interaction between hTRPC1 and 
      hTRPC6, and also between both hTRPCs and the type II IP3 receptor (IP3RII). The 
      latter was greater after treatment with TG. TBHQ-induced coupling between hTRPC1 
      and 6 was transient and decreased after 30s of treatment, while that induced by 
      TG increased for at least 3 min. TBHQ induced association between SERCA3, located 
      in the acidic stores, hTRPC1, hTRPC6 and Orai1. TBHQ also evoked coupling between 
      SERCA3 and IP3RII, presumably located in the DTS, thus suggesting interplay 
      between both Ca2+ stores. Similarly, TG induces the interaction of SERCA2b with 
      hTRPC1 and 6 and the IP3RII. The interactions between hTRPC1, hTRPC6, IP3RII and 
      SERCA3 were impaired by disruption of the microtubules, supporting a role for 
      microtubules in Ca2+ homeostasis. In conclusion, the present data demonstrate for 
      the first time that hTRPC1, hTRPC6, IP3RII and SERCA3 are parts of a 
      macromolecular protein complex activated by depletion of the intracellular Ca2+ 
      stores in human platelets.
FAU - Redondo, Pedro C
AU  - Redondo PC
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      CB2 3EG Cambridge, UK. pcr@unex.es
FAU - Jardin, Isaac
AU  - Jardin I
FAU - Lopez, Jose J
AU  - Lopez JJ
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
DEP - 20071223
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroquinones)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC6 Cation Channel)
RN  - 0 (TRPC6 protein, human)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - 26XK13B61B (2,5-di-tert-butylhydroquinone)
RN  - 60GCX7Y6BH (Flufenamic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 7.2.2.10 (ATP2A3 protein, human)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Blood Platelets/drug effects/*metabolism
MH  - Blotting, Western
MH  - Calcium/*metabolism
MH  - Calcium Signaling/drug effects
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cell Membrane/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Electroporation
MH  - Enzyme Inhibitors/pharmacology
MH  - Flufenamic Acid/pharmacology
MH  - Humans
MH  - Hydroquinones/pharmacology
MH  - Immunoprecipitation
MH  - Inositol 1,4,5-Trisphosphate Receptors/*metabolism
MH  - Microtubules/drug effects/*metabolism
MH  - Protein Binding
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/*metabolism
MH  - TRPC Cation Channels/*metabolism
MH  - TRPC6 Cation Channel
MH  - Thapsigargin/pharmacology
EDAT- 2008/01/15 09:00
MHDA- 2008/08/01 09:00
CRDT- 2008/01/15 09:00
PHST- 2007/10/18 00:00 [received]
PHST- 2007/12/11 00:00 [revised]
PHST- 2007/12/11 00:00 [accepted]
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/08/01 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - S0167-4889(07)00313-8 [pii]
AID - 10.1016/j.bbamcr.2007.12.008 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2008 Jun;1783(6):1163-76. doi: 
      10.1016/j.bbamcr.2007.12.008. Epub 2007 Dec 23.