Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides

Marek K. Korzeniowski, Marko A. Popovic, Zsofia Szentpetery, P. Várnai, Stanko S. Stojilkovic, Tomas Balla

Research output: Article

101 Citations (Scopus)

Abstract

Recent studies identified two main components of store-operated calcium entry (SOCE): the endoplasmic reticulum-localized Ca2+ sensor protein, STIM1, and the plasma membrane (PM)-localized Ca2+ channel, Orai1/CRACM1. In the present study, we investigated the phosphoinositide dependence of Orai1 channel activation in the PM and of STIM1 movements from the tubular to PM-adjacent endoplasmic reticulum regions during Ca2+ store depletion. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) levels were changed either with agonist stimulation or by chemically induced recruitment of a phosphoinositide 5-phosphatase domain to the PM, whereas PtdIns4P levels were decreased by inhibition or down-regulation of phosphatidylinositol 4-kinases (PI4Ks). Agonist-induced phospholipase C activation and PI4K inhibition, but not isolated PtdIns(4,5)P2 depletion, substantially reduced endogenous or STIM1/Orai1-mediated SOCE without preventing STIM1 movements toward the PM upon Ca2+ store depletion. Patch clamp analysis of cells overexpressing STIM1 and Orai1 proteins confirmed that phospholipase C activation or PI4K inhibition greatly reduced ICRAC currents. These results suggest an inositide requirement of Orai1 activation but not STIM1 movement and indicate that PtfIns4P rather than PtdIns(4,5)P2 is a likely determinant of Orai1 channel activity.

Original languageEnglish
Pages (from-to)21027-21035
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number31
DOIs
Publication statusPublished - júl. 31 2009

Fingerprint

Cell membranes
Phosphatidylinositols
Phosphatidylinositol 4,5-Diphosphate
Cell Membrane
1-Phosphatidylinositol 4-Kinase
Calcium
Chemical activation
phosphoinositide 5-phosphatase
Type C Phospholipases
Endoplasmic Reticulum
Clamping devices
Proteins
Down-Regulation
Sensors
Stromal Interaction Molecule 1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Korzeniowski, M. K., Popovic, M. A., Szentpetery, Z., Várnai, P., Stojilkovic, S. S., & Balla, T. (2009). Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides. Journal of Biological Chemistry, 284(31), 21027-21035. https://doi.org/10.1074/jbc.M109.012252

Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides. / Korzeniowski, Marek K.; Popovic, Marko A.; Szentpetery, Zsofia; Várnai, P.; Stojilkovic, Stanko S.; Balla, Tomas.

In: Journal of Biological Chemistry, Vol. 284, No. 31, 31.07.2009, p. 21027-21035.

Research output: Article

Korzeniowski, MK, Popovic, MA, Szentpetery, Z, Várnai, P, Stojilkovic, SS & Balla, T 2009, 'Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides', Journal of Biological Chemistry, vol. 284, no. 31, pp. 21027-21035. https://doi.org/10.1074/jbc.M109.012252
Korzeniowski, Marek K. ; Popovic, Marko A. ; Szentpetery, Zsofia ; Várnai, P. ; Stojilkovic, Stanko S. ; Balla, Tomas. / Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 31. pp. 21027-21035.
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