Home LiteratureArticle Details
PMID: 17925382 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Role of the microtubule cytoskeleton in the function of the store-operated Ca2+ channel activator STIM1.

Journal of cell science ·Vol. 120 ·No. Pt 21 ·2007-11-01 ·Pages 3762-71

Smyth JT, DeHaven WI, Bird GS, Putney JW

Abstract

We examined the role of the microtubule cytoskeleton in the localization and store-operated Ca(2+) entry (SOCE) function of the endoplasmic reticulum (ER) Ca(2+) sensor stromal interaction molecule 1 (STIM1) in HEK 293 cells. STIM1 tagged with an enhanced yellow fluorescent protein (EYFP-STIM1) exhibited a fibrillar localization that colocalized with endogenous alpha-tubulin. Depolymerization of microtubules with nocodazole caused a change from a fibrillar EYFP-STIM1 localization to one that was similar to that of the ER. Treatment of HEK 293 cells with nocodazole had a detrimental impact on SOCE and the associated Ca(2+) release-activated Ca(2+) current (I(CRAC)). This inhibition was significantly reversed in cells overexpressing EYFP-STIM1, implying that the primary inhibitory effect of nocodazole is related to STIM1 function. Surprisingly, nocodazole treatment alone induced significant SOCE and I(CRAC) in cells expressing EYFP-STIM1, and this was accompanied by an increase in EYFP-STIM1 fluorescence near the plasma membrane. We conclude that microtubules play a facilitative role in the SOCE signaling pathway by optimizing the localization of STIM1.

MeSH Terms
Calcium/metabolism Calcium Channels/metabolism Calcium Signaling/physiology Cell Line Cytoskeleton/metabolism Endoplasmic Reticulum/metabolism Humans Membrane Proteins/genetics,metabolism Microtubules/metabolism Neoplasm Proteins/genetics,metabolism Nocodazole/metabolism Patch-Clamp Techniques Recombinant Fusion Proteins/genetics,metabolism Stromal Interaction Molecule 1 Tubulin/metabolism Tubulin Modulators/metabolism
Chemicals
Calcium Channels Membrane Proteins Neoplasm Proteins Recombinant Fusion Proteins STIM1 protein, human Stromal Interaction Molecule 1 Tubulin Tubulin Modulators Nocodazole Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Smyth Jeremy T
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, Department of Health and Human Services, PO Box 12233, Research Triangle Park, NC 27709, USA.
DeHaven Wayne I
Bird Gary S
Putney James W
References (25)
25 references, click to expand
  1. Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai.
    Nature. 2006 Sep 14;443(7108):226-9 PMID: 16921385
  2. An examination of the secretion-like coupling model for the activation of the Ca2+ release-activated Ca2+ current I(CRAC) in RBL-1 cells.
    J Physiol. 2001 Apr 1;532(Pt 1):55-71 PMID: 11283225
  3. Amplification of CRAC current by STIM1 and CRACM1 (Orai1).
    Nat Cell Biol. 2006 Jul;8(7):771-3 PMID: 16733527
  4. Role of the cytoskeleton in calcium signaling in NIH 3T3 cells. An intact cytoskeleton is required for agonist-induced [Ca2+]i signaling, but not for capacitative calcium entry.
    J Biol Chem. 1997 Oct 17;272(42):26555-61 PMID: 9334235
  5. Calcium inhibition and calcium potentiation of Orai1, Orai2, and Orai3 calcium release-activated calcium channels.
    J Biol Chem. 2007 Jun 15;282(24):17548-56 PMID: 17452328
  6. Submaximal stimulation of porcine endothelial cells causes focal Ca2+ elevation beneath the cell membrane.
    J Physiol. 1998 Jan 1;506 ( Pt 1):109-25 PMID: 9481676
  7. STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane.
    Nature. 2005 Oct 6;437(7060):902-5 PMID: 16208375
  8. Microtubules and the endoplasmic reticulum are highly interdependent structures.
    J Cell Biol. 1986 Oct;103(4):1557-68 PMID: 3533956
  9. Microtubule disruption suppresses allergic response through the inhibition of calcium influx in the mast cell degranulation pathway.
    J Immunol. 2005 Apr 15;174(8):4584-9 PMID: 15814680
  10. Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells.
    J Physiol. 2005 Feb 1;562(Pt 3):697-706 PMID: 15513935
  11. Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane.
    J Cell Biol. 2006 Sep 11;174(6):803-13 PMID: 16966422
  12. CRACM1 multimers form the ion-selective pore of the CRAC channel.
    Curr Biol. 2006 Oct 24;16(20):2073-9 PMID: 16978865
  13. Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1.
    J Biol Chem. 2006 Aug 25;281(34):24979-90 PMID: 16807233
  14. Aggregation of STIM1 underneath the plasma membrane induces clustering of Orai1.
    Biochem Biophys Res Commun. 2006 Dec 1;350(4):969-76 PMID: 17045966
  15. The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions.
    J Cell Biol. 2006 Sep 11;174(6):815-25 PMID: 16966423
  16. Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum.
    Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16704-9 PMID: 17075073
  17. Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane.
    J Biol Chem. 2006 Dec 29;281(52):40302-9 PMID: 17056596
  18. Biochemical properties and cellular localisation of STIM proteins.
    Cell Calcium. 2007 Aug;42(2):123-32 PMID: 17382385
  19. Store-operated Ca2+ entry: evidence for a secretion-like coupling model.
    Cell. 1999 Aug 20;98(4):487-99 PMID: 10481913
  20. STIM1, an essential and conserved component of store-operated Ca2+ channel function.
    J Cell Biol. 2005 May 9;169(3):435-45 PMID: 15866891
  21. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx.
    Curr Biol. 2005 Jul 12;15(13):1235-41 PMID: 16005298
  22. Functional homogeneity of the non-mitochondrial Ca2+ pool in intact mouse lacrimal acinar cells.
    J Biol Chem. 1992 Sep 15;267(26):18382-6 PMID: 1382054
  23. Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity.
    Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9357-62 PMID: 16751269
  24. Dissociation of regulated trafficking of TRPC3 channels to the plasma membrane from their activation by phospholipase C.
    J Biol Chem. 2006 Apr 28;281(17):11712-20 PMID: 16522635
  25. Biochemical and functional characterization of Orai proteins.
    J Biol Chem. 2007 Jun 1;282(22):16232-43 PMID: 17293345
Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
0021-9533
DOI
10.1242/jcs.015735
Published
2007-11-01
Epub
2007-00-09
Pages
3762-71
Language
English
Region
England
NLM ID
0052457
PMCID
PMC2440341
Subset
IM
Grants
Intramural NIH HHS · Z01 ES090087-11 · United States
Intramural NIH HHS · Z99 ES999999 · United States
External Links
PubMed source DOI: 10.1242/jcs.015735 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2