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The inositol 1,4,5-trisphosphate receptor (InsP3R) plays a key role in intracellular Ca2+ signaling. InsP3R is activated by InsP3 produced from phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C cleavage. Using planar lipid bilayer reconstitution technique, we demonstrate here that rat cerebellar InsP3R forms a stable inhibitory complex with endogenous PIP2. Disruption of InsP3R-PIP2 interaction by specific anti-PIP2 monoclonal antibody resulted in 3-4-fold increase in InsP3R activity and 10-fold shift in apparent affinity for InsP3. Exogenously added PIP2 blocks InsP3 binding to InsP3R and inhibits InsP3R activity. Similar results were obtained with a newly synthesized water soluble analog of PIP2, dioctanoyl-(4,5)PIP2, indicating that insertion of PIP2 into membrane is not required to exert its inhibitory effects on the InsP3R. We hypothesize that the functional link between InsP3R and PIP2 described in the present report provides a basis for a local, rapid, and efficient coupling between phospholipase C activation, PIP2 hydrolysis, and intracellular Ca2+ wave initiation in neuronal and non-neuronal cells.
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
February 2006,
Proceedings of the National Academy of Sciences of the United States of America,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
March 2000,
Molecular cell biology research communications : MCBRC,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
June 1987,
Endocrinology,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
January 1993,
Visual neuroscience,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
February 2000,
The Journal of biological chemistry,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
June 2001,
Plant physiology,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
September 1986,
The Biochemical journal,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
March 1993,
Trends in pharmacological sciences,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
August 1993,
Biochemical and biophysical research communications,
V D Lupu, and
E Kaznacheyeva, and
U M Krishna, and
J R Falck, and
I Bezprozvanny
August 2004,
The Journal of biological chemistry,
