EB1 binding restricts STIM1 translocation to ER-PM junctions and regulates store-operated Ca
| Autor: | Chi-Lun, Chang, Yu-Ju, Chen, Carlo Giovanni, Quintanilla, Ting-Sung, Hsieh, Jen, Liou |
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| Rok vydání: | 2017 |
| Předmět: |
inorganic chemicals
ORAI1 Protein Cell Membrane Endoplasmic Reticulum Microtubules Models Biological Article Protein Transport Humans Calcium Amino Acid Sequence Calcium Channels Calcium Signaling Stromal Interaction Molecule 1 Microtubule-Associated Proteins Research Articles HeLa Cells Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | STIM1 activates store-operated Ca2+ entry (SOCE) by translocating to endoplasmic reticulum–plasma membrane junctions. Chang et al. reveal that STIM1 localization and SOCE are regulated by a dynamic trapping mechanism mediated by STIM1 binding to EB1 at growing microtubule ends. The endoplasmic reticulum (ER) Ca2+ sensor STIM1 forms oligomers and translocates to ER–plasma membrane (PM) junctions to activate store-operated Ca2+ entry (SOCE) after ER Ca2+ depletion. STIM1 also interacts with EB1 and dynamically tracks microtubule (MT) plus ends. Nevertheless, the role of STIM1–EB1 interaction in regulating SOCE remains unresolved. Using live-cell imaging combined with a synthetic construct approach, we found that EB1 binding constitutes a trapping mechanism restricting STIM1 targeting to ER–PM junctions. We further showed that STIM1 oligomers retain EB1 binding ability in ER Ca2+-depleted cells. By trapping STIM1 molecules at dynamic contacts between the ER and MT plus ends, EB1 binding delayed STIM1 translocation to ER–PM junctions during ER Ca2+ depletion and prevented excess SOCE and ER Ca2+ overload. Our study suggests that STIM1–EB1 interaction shapes the kinetics and amplitude of local SOCE in cellular regions with growing MTs and contributes to spatiotemporal regulation of Ca2+ signaling crucial for cellular functions and homeostasis. |
| Databáze: | OpenAIRE |
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