Please use this identifier to cite or link to this item:
Title: Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry.
Authors: Albarran, Letizia
Lopez, Jose J
Amor, Nidhal Ben
Martin-Cano, Francisco E
Berna-Erro, Alejandro
Smani, Tarik
Salido, Gines M
Rosado, Juan A
metadata.dc.subject.mesh: Calcium
Intracellular Calcium-Sensing Proteins
Membrane Proteins
Neoplasm Proteins
ORAI1 Protein
Protein Interaction Mapping
Protein Interaction Maps
Stromal Interaction Molecule 1
Issue Date: 12-Apr-2016
Abstract: Ca(2+) influx by store-operated Ca(2+) channels is a major mechanism for intracellular Ca(2+) homeostasis and cellular function. Here we present evidence for the dynamic interaction between the SOCE-associated regulatory factor (SARAF), STIM1 and Orai1. SARAF overexpression attenuated SOCE and the STIM1-Orai1 interaction in cells endogenously expressing STIM1 and Orai1 while RNAi-mediated SARAF silencing induced opposite effects. SARAF impaired the association between Orai1 and the Orai1-activating small fragment of STIM1 co-expressed in the STIM1-deficient NG115-401L cells. Cell treatment with thapsigargin or physiological agonists results in direct association of SARAF with Orai1. STIM1-independent interaction of SARAF with Orai1 leads to activation of this channel. In cells endogenously expressing STIM1 and Orai1, Ca(2+) store depletion leads to dissociation of SARAF with STIM1 approximately 30s after treatment with thapsigargin, which paralleled the increase in SARAF-Orai1 interaction, followed by reinteraction with STIM1 and dissociation from Orai1. Co-expression of SARAF and either Orai1 or various N-terminal deletion Orai1 mutants did not alter SARAF-Orai1 interaction; however, expression of C-terminal deletion Orai1 mutants or blockade of the C-terminus of Orai1 impair the interaction with SARAF. These observations suggest that SARAF exerts an initial positive role in the activation of SOCE followed by the facilitation of SCDI of Orai1.
metadata.dc.identifier.doi: 10.1038/srep24452
Appears in Collections:Producción 2020

Files in This Item:
File SizeFormat 
PMC4828706.pdf1,38 MBAdobe PDFView/Open

This item is protected by original copyright

This item is licensed under a Creative Commons License Creative Commons