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The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and store-operated calcium entry (SOCE)

Giurisato, E
•
Gamberucci, A.
•
Ulivieri, C.
altro
Sorrentino, V.
2014
  • journal article

Periodico
MOLECULAR BIOLOGY OF THE CELL
Abstract
Store-operated calcium entry (SOCE) is the predominant Ca2+ entry mechanism in nonexcitable cells and controls a variety of physiological and pathological processes. Although significant progress has been made in identifying the components required for SOCE, the molecular mechanisms underlying it are elusive. The present study provides evidence for a direct involvement of kinase suppressor of Ras 2 (KSR2) in SOCE. Using lymphocytes and fibroblasts from ksr2−/− mice and shKSR2-depleted cells, we find that KSR2 is critical for the elevation of cytosolic Ca2+ concentration. Specifically, our results show that although it is dispensable for Ca2+-store depletion, KSR2 is required for optimal calcium entry. We observe that KSR2 deficiency affects stromal interaction molecule 1 (STIM1)/ORAI1 puncta formation, which is correlated with cytoskeleton disorganization. Of interest, we find that KSR2-associated calcineurin is crucial for SOCE. Blocking calcineurin activity impairs STIM1/ORAI1 puncta-like formation and cytoskeleton organization. In addition, we observe that calcineurin activity and its role in SOCE are both KSR2 dependent.
DOI
10.1091/mbc.E13-05-0292
WOS
WOS:000339651000007
SCOPUS
2-s2.0-84901650313
Archivio
http://hdl.handle.net/11368/2910300
http://www.molbiolcell.org/content/25/11/1769.full.pdf+html
Diritti
metadata only access
Soggetti
  • Animals

  • COS Cells

  • Calcineurin

  • Calcium

  • Calcium Channels

  • Cell Nucleus

  • Cercopithecus aethiop...

  • Cytoskeleton

  • Gene Knockout Techniq...

  • HeLa Cells

  • Humans

  • Intracellular Space

  • Lymphocytes

  • Membrane Proteins

  • Mice

  • NFATC Transcription F...

  • Neoplasm Proteins

  • ORAI1 Protein

  • Protein Transport

  • Protein-Serine-Threon...

  • Stromal Interaction M...

  • Thapsigargin

  • Molecular Biology

  • Cell Biology

  • Medicine (all)

Web of Science© citazioni
15
Data di acquisizione
Jun 16, 2022
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