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STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM Junctions

Krishna Prasad Subedi1, Hwei Ling Ong1, Ga-Yeon Son1

  • 1Secretory Physiology Section, NIDCR, NIH, Bethesda, MD 20892, USA.

Cell Reports
|April 12, 2018
PubMed

Insights

Stromal interaction molecule 2 (STIM2) traps STIM1, enhancing calcium (Ca2+) entry through Orai1 channels. This improves cellular responses and transcription factor activation, crucial for cell function.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Orai1 calcium channels mediate critical Ca2+ signals for cell function.
  • Stromal interaction molecule 1 (STIM1) activates Orai1 at ER-PM junctions.
  • The role of STIM2 in Orai1 activation and cell signaling is unclear.

Purpose of the Study:

  • To elucidate the physiological role of STIM2 in regulating STIM1/Orai1 channel function.
  • To investigate how STIM2 influences the conformation and activation of STIM1.
  • To understand STIM2's contribution to calcium signaling and cellular responses.

Main Methods:

  • Utilized conformational sensors for STIM1 and STIM2.
  • Performed protein interaction studies.
  • Conducted functional assays to measure Ca2+ entry and NFAT activation.

Main Results:

  • STIM2 is constitutively present in ER-PM junctions when ER Ca2+ stores are replete.
  • STIM2 traps STIM1, inducing a conformational change that enhances STIM1/Orai1 coupling.
  • STIM2 amplifies Orai1-mediated Ca2+ influx, boosting NFAT activation at low agonist concentrations.

Conclusions:

  • STIM2 plays a critical role in inducing the activated conformation of STIM1.
  • STIM2 modulates STIM1/Orai1 function to fine-tune receptor-evoked Ca2+ signaling.
  • STIM2 enhances the fidelity of cellular responses to external stimuli.

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