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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...

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Detalles Bibliográficos
Autores principales: Micheva, Kristina D., Holz, Ronald W., Smith, Stephen J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
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.
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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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