Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/6402
Title: The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and Store-Operated Calcium Entry (SOCE).
Authors: Giurisato, Emanuele 
Gamberucci, Alessandra
Ulivieri, Cristina
Marruganti, S
Rossi, E
Giacomello, Emiliana
Randazzo, Davide
Sorrentino, Vincenzo
Keywords: KSR2, SOCE, Calcium signaling, scaffold molecule,
Issue Date: 2014
Project: None 
Journal: 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 to identify the components required for SOCE, the molecular mechanisms underlying SOCE are still 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 found that KSR2 is critical for the elevation of [Ca2+]i. Specifically, our results show that while it is dispensable for Ca2+ store depletion, KSR2 is required for optimal calcium entry. We observed that KSR2 deficiency affects STIM1/ORAI1 puncta formation, which is correlated to cytoskeleton disorganization. Interestingly, we found that KSR2-associated calcineurin is crucial for SOCE. Blocking calcineurin activity impaired STIM1/ORAI1 puncta-like formation and cytoskeleton organization. In addition, we observed that calcineurin activity and its role on SOCE were both KSR2-dependent.These findings identify KSR2 as a regulator of SOCE and reveal a new mechanism whereby the KSR2-calcineurin complex is crucial in the store dependent STIM1-ORAI1 dynamics.
Description: 
59920
URI: http://hdl.handle.net/20.500.12779/6402
ISSN: 1059-1524
DOI: 10.1091/mbc.E13-05-0292
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