scholarly journals T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis.

1997 ◽  
Vol 17 (6) ◽  
pp. 3005-3012 ◽  
Author(s):  
T Jayaraman ◽  
A R Marks

The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) calcium release channel is present on the endoplasmic reticulum of most cell types. T lymphocytes which have been made deficient in IP3R1 lack detectable IP3-induced intracellular calcium release and exhibit defective signaling via the T-cell receptor (TCR) (T. Jayaraman, E. Ondriasova, K. Ondrias, D. Harnick, and A. R. Marks, Proc. Natl. Acad. Sci. USA 92:6007-6011, 1995). We now show that IP3R1-deficient T cells are resistant to apoptosis induced by dexamethasone, TCR stimulation, ionizing radiation, and Fas. Resistance to TCR-mediated apoptosis in IP3R1-deficient cells is reversed by pharmacologically raising cytoplasmic calcium levels. TCR-mediated apoptosis can be induced in calcium-free media, indicating that extracellular calcium influx is not required. These findings suggest that intracellular calcium release via the IP3R1 is a critical mediator of apoptosis.

2005 ◽  
Vol 280 (16) ◽  
pp. 15912-15920 ◽  
Author(s):  
Dan J. Bare ◽  
Claudia S. Kettlun ◽  
Mei Liang ◽  
Donald M. Bers ◽  
Gregory A. Mignery

The type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2) was identified previously as the predominant isoform in cardiac ventricular myocytes. Here we reported the subcellular localization of InsP3R2 to the cardiomyocyte nuclear envelope (NE). The other major known endo/sarcoplasmic reticulum calcium-release channel (ryanodine receptor) was not localized to the NE, indicating functional segregation of these channels and possibly a unique role for InsP3R2 in regulating nuclear calcium dynamics. Immunoprecipitation experiments revealed that the NE InsP3R2 associates with Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ), the major isoform expressed in cardiac myocytes. Recombinant InsP3R2 and CaMKIIδBalso co-immunoprecipitated after co-expression in COS-1 cells. Additionally, the amino-terminal 1078 amino acids of the InsP3R2 were sufficient for interaction with CaMKIIδBand associated upon mixing following separate expression. CaMKII can also phosphorylate InsP3R2, as demonstrated by32P labeling. Incorporation of CaMKII-treated InsP3R2 into planar lipid bilayers revealed that InsP3-mediated channel open probability is significantly reduced (∼11 times) by phosphorylation via CaMKII. We concluded that the InsP3R2 and CaMKIIδ likely represent two central components of a multiprotein signaling complex, and this raises the possibility that calcium release via InsP3R2 in the myocyte NE may activate local CaMKII signaling, which may feedback on InsP3R2 function.


2002 ◽  
Vol 4 (3) ◽  
pp. 191-197 ◽  
Author(s):  
Peter Koulen ◽  
Yiqiang Cai ◽  
Lin Geng ◽  
Yoshiko Maeda ◽  
Sayoko Nishimura ◽  
...  

2017 ◽  
Vol 439 ◽  
pp. 308-316 ◽  
Author(s):  
Marlena Schoenberg Fejzo ◽  
Ronny Myhre ◽  
Lucía Colodro-Conde ◽  
Kimber W. MacGibbon ◽  
Janet S. Sinsheimer ◽  
...  

1999 ◽  
Vol 206 (2) ◽  
pp. 163-177 ◽  
Author(s):  
Nora Rosemblit ◽  
Maria C. Moschella ◽  
Elena Ondria s̆ ◽  
David E. Gutstein ◽  
Karol Ondria s̆ ◽  
...  

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