Signaling microdomains regulate inositol 1,4,5-trisphosphate-mediated intracellular calcium transients in cultured neurons.
Standard
Signaling microdomains regulate inositol 1,4,5-trisphosphate-mediated intracellular calcium transients in cultured neurons. / Jacob, Simon N; Choe, Chi-Un; Uhlen, Per; DeGray, Brenda; Yeckel, Mark F; Ehrlich, Barbara E.
In: J NEUROSCI, Vol. 25, No. 11, 11, 2005, p. 2853-2864.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Signaling microdomains regulate inositol 1,4,5-trisphosphate-mediated intracellular calcium transients in cultured neurons.
AU - Jacob, Simon N
AU - Choe, Chi-Un
AU - Uhlen, Per
AU - DeGray, Brenda
AU - Yeckel, Mark F
AU - Ehrlich, Barbara E
PY - 2005
Y1 - 2005
N2 - Ca2+ signals in neurons use specific temporal and spatial patterns to encode unambiguous information about crucial cellular functions. To understand the molecular basis for initiation and propagation of inositol 1,4,5-trisphosphate (InsP3)-mediated intracellular Ca2+ signals, we correlated the subcellular distribution of components of the InsP3 pathway with measurements of agonist-induced intracellular Ca2+ transients in cultured rat hippocampal neurons and pheochromocytoma cells. We found specialized domains with high levels of phosphatidylinositol-4-phosphate kinase (PIPKI) and chromogranin B (CGB), proteins acting synergistically to increase InsP3 receptor (InsP3R) activity and sensitivity. In contrast, Ca2+ pumps in the plasma membrane (PMCA) and sarco-endoplasmic reticulum as well as buffers that antagonize the rise in intracellular Ca2+ were distributed uniformly. By pharmacologically blocking phosphatidylinositol-4-kinase and PIPKI or disrupting the CGB-InsP3R interaction by transfecting an interfering polypeptide fragment, we produced major changes in the initiation site and kinetics of the Ca2+ signal. This study shows that a limited number of proteins can reassemble to form unique, spatially restricted signaling domains to generate distinctive signals in different regions of the same neuron. The finding that the subcellular location of initiation sites and protein microdomains was cell type specific will help to establish differences in spatiotemporal Ca2+ signaling in different types of neurons.
AB - Ca2+ signals in neurons use specific temporal and spatial patterns to encode unambiguous information about crucial cellular functions. To understand the molecular basis for initiation and propagation of inositol 1,4,5-trisphosphate (InsP3)-mediated intracellular Ca2+ signals, we correlated the subcellular distribution of components of the InsP3 pathway with measurements of agonist-induced intracellular Ca2+ transients in cultured rat hippocampal neurons and pheochromocytoma cells. We found specialized domains with high levels of phosphatidylinositol-4-phosphate kinase (PIPKI) and chromogranin B (CGB), proteins acting synergistically to increase InsP3 receptor (InsP3R) activity and sensitivity. In contrast, Ca2+ pumps in the plasma membrane (PMCA) and sarco-endoplasmic reticulum as well as buffers that antagonize the rise in intracellular Ca2+ were distributed uniformly. By pharmacologically blocking phosphatidylinositol-4-kinase and PIPKI or disrupting the CGB-InsP3R interaction by transfecting an interfering polypeptide fragment, we produced major changes in the initiation site and kinetics of the Ca2+ signal. This study shows that a limited number of proteins can reassemble to form unique, spatially restricted signaling domains to generate distinctive signals in different regions of the same neuron. The finding that the subcellular location of initiation sites and protein microdomains was cell type specific will help to establish differences in spatiotemporal Ca2+ signaling in different types of neurons.
M3 - SCORING: Zeitschriftenaufsatz
VL - 25
SP - 2853
EP - 2864
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 11
M1 - 11
ER -