ID 111483
Author
Morita, Takao Health Sciences University of Hokkaido
Tanimura, Akihiko Health Sciences University of Hokkaido
Baba, Yoshihiro Osaka University
Kurosaki, Tomohiro Osaka University
Tojyo, Yosuke Health Sciences University of Hokkaido
Keywords
Ca2+ entry
Ca2+ store
Stim1
B cell receptor
tyrosine kinase
Content Type
Journal Article
Description
In most non-excitable cells, the depletion of intracellular Ca2+ stores activates capacitative Ca2+ entry (CCE), which is a Ca2+-selective and La3+-sensitive entry pathway. Here, we report a novel mechanism of La3+-resistant Ca2+ entry that is synergistically regulated by B cell receptor (BCR) stimulation and Ca2+ store depletion (B-SOC). In the wildtype (WT) DT40 cells, BCR stimulation with anti-IgM antibodies induced Ca2+ release and subsequent Ca2+ entry in the presence of 0.3 μMLa3+ which blocks CCE completely. In the inositol 1,4,5-trisphosphate receptor-deficient (IP3R-KO) cells, BCR stimulation elicited neither Ca2+ release nor Ca2+ entry. However, under pretreatment of thapsigargin (ThG), BCR stimulation induced La3+-resistant Ca2+ entry into both WT and IP3R-KO cells. These results indicate that BCR stimulation and Ca2+ store depletion work in concert to activate the La3+-resistant Ca2+ entry pathway. B-SOC was inhibited by tyrosine kinase inhibitor, genistein. In addition, B-SOC was completely abolished in Stim1-deficient cells and was restored by overexpression of yellow fluorescent protein (YFP)-tagged Stim1, but was unaffected by double knockdown of Orai1/Orai2. These results demonstrate a unique non-CCE pathway, in which Ca2+ entry depends on Stim1 and tyrosine kinase activation. It is likely that similar regulation of Ca2+ entry occurs in other cell types including salivary gland cells.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
56
Issue
Supplement
Start Page
383
End Page
387
Sort Key
383
Published Date
2009-12
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher