EFHB is a Novel Cytosolic Ca2+ Sensor That Modulates STIM1-SARAF Interaction
| Autor: | Tarik Smani, Jose J. Lopez, Alejandro Berna-Erro, Ginés M. Salido, Pedro J. Camello, Letizia Albarran, Jose Sanchez-Collado, Isaac Jardin, Juan A. Rosado |
|---|---|
| Přispěvatelé: | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
inorganic chemicals Orai1 Physiology STIM1 lcsh:Physiology Calcium entry lcsh:Biochemistry 03 medical and health sciences Cytosol Intracellular Calcium-Sensing Proteins EFHB Humans lcsh:QD415-436 Protein Interaction Maps Stromal Interaction Molecule 1 EF Hand Motifs SARAF Physics lcsh:QP1-981 Membrane Proteins Neoplasm Proteins 030104 developmental biology HEK293 Cells Calcium Humanities HeLa Cells |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 3, Pp 1164-1178 (2018) idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) idUS. Depósito de Investigación de la Universidad de Sevilla instname |
| Popis: | 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. MINECO BFU2013-45564-C2-1-P/2-P, BFU2016-74932-C2-1-P/2-P, BFU2016-74932-C2-1-P Junta de Extremadura-FEDER (Fondo Europeo de Desarrollo Regional Grants) IB16046, GR18061 Junta de Extremadura-FEDER European Union (EU) IB16046 Ministerio Economía y Competitividad, España IJCI-2015-25665 MINECO Grant BFU2016-74932-C2-1-P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|