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EFHB is a Novel Cytosolic Ca2+ Sensor That Modulates STIM1-SARAF Interaction

Authors
  • Albarran, Letizia
  • Lopez, Jose J.
  • Jardin, Isaac
  • Sanchez-Collado, Jose
  • Berna-Erro, Alejandro
  • Smani, Tarik
  • Camello, Pedro J.
  • Salido, Gines M.
  • Rosado, Juan A.
Type
Published Article
Journal
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Publication Date
Nov 27, 2018
Volume
51
Issue
3
Pages
1164–1178
Identifiers
DOI: 10.1159/000495494
PMID: 30481768
Source
Karger
Keywords
License
Green
External links

Abstract

Background/Aims: STIM1 and Orai1 are the key components of store-operated Ca2+ entry (SOCE). Among the proteins involved in the regulation of SOCE, SARAF prevents spontaneous activation of SOCE and modulates STIM1 function. Methods: Cytosolic Ca2+ mobilization was estimated in fura-2-loaded cells using an epifluorescence inverted microscope. STIM1 interaction with Orai1, EFHB (EF-hand domain family member B, also known as CFAP21) and SARAF was detected by immunoprecipitation followed by Western blotting using specific antibodies. The involvement of EFHB in the translocation of NFAT to the nucleus was detected by confocal microscopy. Results: Here, we report the identification of EFHB as a new SOCE regulator. EFHB interacts with STIM1 upon store depletion and dissociates through a Ca2+-dependent mechanism. RNAi-mediated silencing as well as overexpression studies revealed that EFHB plays a relevant role in the interaction of STIM1 and Orai1 upon store depletion, the activation of SOCE and NFAT translocation from the cytosol to the nucleus. Silencing EFHB expression abolished the dissociation of SARAF from STIM1, which indicates that EFHB might play an important role in the dynamic interaction between both proteins, which is relevant for the activation of Orai1 channels upon Ca2+ store depletion and their subsequent modulation via slow Ca2+-dependent inactivation. Conclusion: Our results indicate that EFHB is a new SOCE regulator that modulates STIM1-SARAF interaction.

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