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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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The ER/PM microdomain, PI(4,5)P₂ and the regulation of STIM1-Orai1 channel function

Xu Cao1, Seok Choi2, Jozsef J Maléth3

  • 1Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD 20892, United States.

Cell Calcium
|April 7, 2015
PubMed

Insights

Cellular communication occurs in microdomains, with the endoplasmic reticulum (ER) interacting with other organelles. This review explores ER/plasma membrane microdomains and their role in calcium signaling via the Orai1-STIM1 complex.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell signaling pathways are orchestrated within specialized cellular microdomains.
  • The endoplasmic reticulum (ER) is a central organelle in forming these microdomains with other organelles like mitochondria and the plasma membrane.
  • These microdomains facilitate the exchange of ions and lipids between organelles.

Purpose of the Study:

  • To review recent advances in understanding the molecular mechanisms that establish ER/plasma membrane (PM) microdomains.
  • To elucidate the role of these microdomains in regulating calcium (Ca2+) signaling.
  • To discuss the dynamic targeting of the Orai1-STIM1 complex within these microdomains.

Main Methods:

  • Literature review of recent research on ER/PM microdomains.
  • Analysis of molecular components involved in tethering ER and PM.
  • Examination of the role of phosphoinositides, specifically PI(4,5)P2, in microdomain formation and function.

Main Results:

  • ER/PM microdomains are enriched in PI(4,5)P2, influencing the localization of signaling complexes.
  • The Orai1-STIM1 complex dynamically targets PI(4,5)P2-rich and PI(4,5)P2-poor regions within microdomains.
  • This dynamic targeting is crucial for controlling Orai1 activity and Ca2+ influx, modulated by SARAF.

Conclusions:

  • ER/PM microdomains are critical platforms for receptor-evoked Ca2+ signaling.
  • The precise localization of the Orai1-STIM1 complex within these microdomains dictates its regulatory control.
  • Understanding these molecular interactions provides insights into cellular calcium homeostasis and signaling.
Keywords:
Calcium signalingER/PM microdomainsOrai1Stim1

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