PMID- 17681754
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20151119
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 19
IP  - 10
DP  - 2007 Oct
TI  - Dual role of tubulin-cytoskeleton in store-operated calcium entry in human 
      platelets.
PG  - 2147-54
AB  - Two mechanisms for store-operated Ca(2+) entry (SOCE) regulated by two 
      independent Ca(2+) stores, the dense tubular system (DTS) and the acidic stores, 
      have been described in platelets. We have previously suggested that coupling 
      between the type II IP(3) receptor (IP(3)RII) and hTRPC1, involving 
      reorganization of the actin microfilaments, play an important role in SOCE. 
      However, the involvement of the tubulin microtubules, located beneath the plasma 
      membrane, remains unclear. Here we show that the microtubule disrupting agent 
      colchicine reduced Ca(2+) entry stimulated by low concentrations (0.1 U/mL) of 
      thrombin, which activates SOCE mostly by depleting acidic Ca(2+)-store. 
      Consistently, colchicine reduced SOCE activated by 2,5 
      di-(tertbutyl)-1,4-hydroquinone (TBHQ), which selectively depletes the acidic 
      Ca(2+) stores. In contrast, colchicine enhanced SOCE mediated by depletion of the 
      DTS, induced by high concentrations of thapsigargin (TG), which depletes both the 
      acidic Ca(2+) stores and the DTS, the major releasable Ca(2+) store in platelets. 
      These findings were confirmed by using Sr(2+) as a surrogate for Ca(2+) entry. 
      Colchicine attenuated the coupling between IP(3)RII and hTRPC1 stimulated by 
      thrombin while it enhanced that evoked by TG. Paclitaxel, which induces 
      microtubular stabilization and polymerization, exerted the opposite effects on 
      thrombin- and TG-evoked SOCE and coupling between IP(3)RII and hTRPC1 compared 
      with colchicine. Neither colchicine nor paclitaxel altered the ability of 
      platelets to extrude Ca(2+). These findings suggest that tubulin microtubules 
      play a dual role in SOCE, acting as a barrier that prevents constitutive SOCE 
      regulated by DTS, but also supporting SOCE mediated by the acidic Ca(2+) stores.
FAU - Redondo, Pedro C
AU  - Redondo PC
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, Downing Site, UK. pcr@unex.es
FAU - Harper, Alan G S
AU  - Harper AG
FAU - Sage, Stewart O
AU  - Sage SO
FAU - Rosado, Juan A
AU  - Rosado JA
LA  - eng
GR  - 064070/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070628
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Tubulin)
RN  - 0 (Tubulin Modulators)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - SML2Y3J35T (Colchicine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actin Cytoskeleton/physiology
MH  - Blood Platelets/drug effects/*metabolism/ultrastructure
MH  - Calcium/*metabolism
MH  - Colchicine/pharmacology
MH  - Humans
MH  - Inositol 1,4,5-Trisphosphate Receptors/metabolism
MH  - Ion Transport
MH  - Microtubules/*physiology
MH  - Paclitaxel/pharmacology
MH  - TRPC Cation Channels/metabolism
MH  - Thapsigargin/antagonists & inhibitors
MH  - Thrombin/antagonists & inhibitors
MH  - Tubulin/*physiology
MH  - Tubulin Modulators/pharmacology
EDAT- 2007/08/08 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/08/08 09:00
PHST- 2007/05/29 00:00 [received]
PHST- 2007/06/15 00:00 [accepted]
PHST- 2007/08/08 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/08/08 09:00 [entrez]
AID - S0898-6568(07)00188-X [pii]
AID - 10.1016/j.cellsig.2007.06.011 [doi]
PST - ppublish
SO  - Cell Signal. 2007 Oct;19(10):2147-54. doi: 10.1016/j.cellsig.2007.06.011. Epub 
      2007 Jun 28.