Publication Date:
2022-05-25
Description:
Author Posting. © Society for Neuroscience, 2005. This article is posted here by permission of Society for Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Neuroscience 25 (2005): 2853-2864, doi:10.1523/JNEUROSCI.4313-04.2005.
Description:
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 (PIPKIγ) 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 PIPKIγ 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.
Description:
This work was supported by grants from the National Institutes of Health (GM63496, DK61747 to B.E.E., and
MH67830 to M.F.Y.), Whitehall Foundation (M.F.Y.), German National Merit Foundation (S.N.J. and C.-U.C.), and
Vetenskapsrådet, the Swedish Research Council (P.U.).
Keywords:
InsP3
;
PIPKIγ
;
Chromogranin
;
Signaling microdomain
;
Calcium imaging
;
Hippocampal neurons
Repository Name:
Woods Hole Open Access Server
Type:
Article
Format:
application/pdf
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