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Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity
Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variety of cellular processes, including synaptic vesicle recycling. However, little is known about the spatial distribution of this phospholipid in neurons and its dynamics. In this study, we have focused on these questions by tra...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150764/ https://www.ncbi.nlm.nih.gov/pubmed/11470824 http://dx.doi.org/10.1083/jcb.200102098 |
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author | Micheva, Kristina D. Holz, Ronald W. Smith, Stephen J. |
author_facet | Micheva, Kristina D. Holz, Ronald W. Smith, Stephen J. |
author_sort | Micheva, Kristina D. |
collection | PubMed |
description | Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variety of cellular processes, including synaptic vesicle recycling. However, little is known about the spatial distribution of this phospholipid in neurons and its dynamics. In this study, we have focused on these questions by transiently expressing the phospholipase C (PLC)-δ1 pleckstrin homology (PH) domain fused to green fluorescent protein (GFP) in cultured hippocampal neurons. This PH domain binds specifically and with high affinity to PIP2. Live confocal imaging revealed that in resting cells, PH-GFP is localized predominantly on the plasma membrane. Interestingly, no association of PH-GFP with synaptic vesicles in quiescent neurons was observed, indicating the absence of detectable PIP2 on mature synaptic vesicles. Electrical stimulation of hippocampal neurons resulted in a decrease of the PH-GFP signal at the plasma membrane, most probably due to a PLC-mediated hydrolysis of PIP2. This was accompanied in the majority of presynaptic terminals by a marked increase in the cytoplasmic PH-GFP signal, localized most probably on freshly endocytosed membranes. Further investigation revealed that the increase in PH-GFP signal was dependent on the activation of N-methyl-D-aspartate receptors and the consequent production of nitric oxide (NO). Thus, PIP2 in the presynaptic terminal appears to be regulated by postsynaptic activity via a retrograde action of NO. |
format | Text |
id | pubmed-2150764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21507642008-05-01 Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity Micheva, Kristina D. Holz, Ronald W. Smith, Stephen J. J Cell Biol Research Articles Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variety of cellular processes, including synaptic vesicle recycling. However, little is known about the spatial distribution of this phospholipid in neurons and its dynamics. In this study, we have focused on these questions by transiently expressing the phospholipase C (PLC)-δ1 pleckstrin homology (PH) domain fused to green fluorescent protein (GFP) in cultured hippocampal neurons. This PH domain binds specifically and with high affinity to PIP2. Live confocal imaging revealed that in resting cells, PH-GFP is localized predominantly on the plasma membrane. Interestingly, no association of PH-GFP with synaptic vesicles in quiescent neurons was observed, indicating the absence of detectable PIP2 on mature synaptic vesicles. Electrical stimulation of hippocampal neurons resulted in a decrease of the PH-GFP signal at the plasma membrane, most probably due to a PLC-mediated hydrolysis of PIP2. This was accompanied in the majority of presynaptic terminals by a marked increase in the cytoplasmic PH-GFP signal, localized most probably on freshly endocytosed membranes. Further investigation revealed that the increase in PH-GFP signal was dependent on the activation of N-methyl-D-aspartate receptors and the consequent production of nitric oxide (NO). Thus, PIP2 in the presynaptic terminal appears to be regulated by postsynaptic activity via a retrograde action of NO. The Rockefeller University Press 2001-07-23 /pmc/articles/PMC2150764/ /pubmed/11470824 http://dx.doi.org/10.1083/jcb.200102098 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Micheva, Kristina D. Holz, Ronald W. Smith, Stephen J. Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
title | Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
title_full | Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
title_fullStr | Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
title_full_unstemmed | Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
title_short | Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
title_sort | regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150764/ https://www.ncbi.nlm.nih.gov/pubmed/11470824 http://dx.doi.org/10.1083/jcb.200102098 |
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