Journal
MOLECULES AND CELLS
Volume 35, Issue 1, Pages 41-46Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.1007/s10059-013-2268-7
Keywords
calcium mobilization; Orai1; Stim1; store-operated calcium entry (SOCE); ubiquilin
Categories
Funding
- Next-Generation BioGreen 21 Program, Rural Development Administration, Republic of Korea [PJ008127, PJ008196]
- National Research Foundation of Korea [2012-0005747]
Ask authors/readers for more resources
Store-operated calcium entry (SOCE) channels composed of Stim and Orai proteins play a critical role in diverse biological processes. Upon endoplasmic reticulum (ER)mediated calcium (Ca2+) depletion, Stim proteins oligomerize with Orai to initiate Ca2+ influx across the plasma membrane. The ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of ubiquilin 1 are involved in the degradation of presenilin and polyglutamine proteins. Through screening of Orai1 interaction partner(s) that might have an effect on SOCE, ubiquilin 1 was identified as a target of Orai1. However, the UBL and UBA domains of ubiquilin 1 were dispensable for this interaction. Additionally, ubiquilin 1 and Orai1 colocalized in the cytosolic compartment. Ubiquilin 1 increased the ubiquitination of Orai1, resulting in the formation of a high-molecular-weight form. MG132, a proteasome inhibitor, failed to block the degradation of Orai1, whereas bafilomycin A, a lysosome inhibitor, prevented Orai1 degradation. Confocal microscopy studies demonstrated that a fraction of Orai1 colocalized with ubiquilin 1 and the autophagosomal marker LC3. Because Orai1 is a constituent of SOCE, we determined the effect of ubiquilin 1 on Orai1-mediated Ca2+ influx. As we expected, intracellular Ca2+ mobilization, a process normally potentiated by Orai1, was downregulated by ubiquilin 1. Taken together, these findings suggest that ubiquilin 1 down-regulates intracellular Ca2+ mobilization and its down-stream signaling by promoting the ubiquitination and lysosomal degradation of Orai1.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available