TY - JOUR
T1 - A novel stim1-dependent, non-capacitative Ca2+ entry pathway is activated by B cell receptor stimulation and depletion of Ca2+ stores
AU - Morita, Takao
AU - Tanimura, Akihiko
AU - Baba, Yoshihiro
AU - Kurosaki, Tomohiro
AU - Tojyo, Yosuke
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009
Y1 - 2009
N2 - In most non-excitable cells, the depletion of intracellular Ca2+ stores activates capacitative Ca2+ entry (CCE), which is a Ca 2+-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 Ca 2+ 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 Ca 2+ 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.
AB - In most non-excitable cells, the depletion of intracellular Ca2+ stores activates capacitative Ca2+ entry (CCE), which is a Ca 2+-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 Ca 2+ 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 Ca 2+ 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.
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U2 - 10.2152/jmi.56.383
DO - 10.2152/jmi.56.383
M3 - Article
C2 - 20224233
AN - SCOPUS:77749302167
VL - 56
SP - 383
EP - 387
JO - Journal of Medical Investigation
JF - Journal of Medical Investigation
SN - 1343-1420
IS - SUPPL. 1
ER -