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Signaling microdomains regulate inositol 1,4,5-trisphosphate-mediated intracellular calcium transients in cultured neurons

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dc.contributor.author Jacob, Simon N.
dc.contributor.author Choe, Chi-Un
dc.contributor.author Uhlen, Per
dc.contributor.author DeGray, Brenda
dc.contributor.author Yeckel, Mark F.
dc.contributor.author Ehrlich, Barbara E.
dc.date.accessioned 2009-03-20T18:53:26Z
dc.date.available 2009-03-20T18:53:26Z
dc.date.issued 2005-03-16
dc.identifier.citation Journal of Neuroscience 25 (2005): 2853-2864 en
dc.identifier.uri http://hdl.handle.net/1912/2737
dc.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. en
dc.description.abstract 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. en
dc.description.sponsorship 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.). en
dc.format.mimetype application/pdf
dc.language.iso en_US en
dc.publisher Society for Neuroscience en
dc.relation.uri http://dx.doi.org/10.1523/JNEUROSCI.4313-04.2005
dc.subject InsP3 en
dc.subject PIPKIγ en
dc.subject Chromogranin en
dc.subject Signaling microdomain en
dc.subject Calcium imaging en
dc.subject Hippocampal neurons en
dc.title Signaling microdomains regulate inositol 1,4,5-trisphosphate-mediated intracellular calcium transients in cultured neurons en
dc.type Article en
dc.identifier.doi 10.1523/JNEUROSCI.4313-04.2005


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