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Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis

Active zones are specialized regions of the presynaptic plasma membrane designed for the efficient and repetitive release of neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component of the active zone that is hypothesized to participate both in active zone...

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Autores principales: Leal-Ortiz, Sergio, Waites, Clarissa L., Terry-Lorenzo, Ryan, Zamorano, Pedro, Gundelfinger, Eckart D., Garner, Craig C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396795/
https://www.ncbi.nlm.nih.gov/pubmed/18519737
http://dx.doi.org/10.1083/jcb.200711167
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author Leal-Ortiz, Sergio
Waites, Clarissa L.
Terry-Lorenzo, Ryan
Zamorano, Pedro
Gundelfinger, Eckart D.
Garner, Craig C.
author_facet Leal-Ortiz, Sergio
Waites, Clarissa L.
Terry-Lorenzo, Ryan
Zamorano, Pedro
Gundelfinger, Eckart D.
Garner, Craig C.
author_sort Leal-Ortiz, Sergio
collection PubMed
description Active zones are specialized regions of the presynaptic plasma membrane designed for the efficient and repetitive release of neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component of the active zone that is hypothesized to participate both in active zone formation and the scaffolding of key molecules involved in SV recycling. In this study, we use interference RNAs to eliminate Piccolo expression from cultured hippocampal neurons to assess its involvement in synapse formation and function. Our data show that Piccolo is not required for glutamatergic synapse formation but does influence presynaptic function by negatively regulating SV exocytosis. Mechanistically, this regulation appears to be calmodulin kinase II–dependent and mediated through the modulation of Synapsin1a dynamics. This function is not shared by the highly homologous protein Bassoon, which indicates that Piccolo has a unique role in coupling the mobilization of SVs in the reserve pool to events within the active zone.
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spelling pubmed-23967952008-12-02 Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis Leal-Ortiz, Sergio Waites, Clarissa L. Terry-Lorenzo, Ryan Zamorano, Pedro Gundelfinger, Eckart D. Garner, Craig C. J Cell Biol Research Articles Active zones are specialized regions of the presynaptic plasma membrane designed for the efficient and repetitive release of neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component of the active zone that is hypothesized to participate both in active zone formation and the scaffolding of key molecules involved in SV recycling. In this study, we use interference RNAs to eliminate Piccolo expression from cultured hippocampal neurons to assess its involvement in synapse formation and function. Our data show that Piccolo is not required for glutamatergic synapse formation but does influence presynaptic function by negatively regulating SV exocytosis. Mechanistically, this regulation appears to be calmodulin kinase II–dependent and mediated through the modulation of Synapsin1a dynamics. This function is not shared by the highly homologous protein Bassoon, which indicates that Piccolo has a unique role in coupling the mobilization of SVs in the reserve pool to events within the active zone. The Rockefeller University Press 2008-06-02 /pmc/articles/PMC2396795/ /pubmed/18519737 http://dx.doi.org/10.1083/jcb.200711167 Text en © 2008 Leal-Ortiz et al. 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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Leal-Ortiz, Sergio
Waites, Clarissa L.
Terry-Lorenzo, Ryan
Zamorano, Pedro
Gundelfinger, Eckart D.
Garner, Craig C.
Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
title Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
title_full Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
title_fullStr Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
title_full_unstemmed Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
title_short Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
title_sort piccolo modulation of synapsin1a dynamics regulates synaptic vesicle exocytosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396795/
https://www.ncbi.nlm.nih.gov/pubmed/18519737
http://dx.doi.org/10.1083/jcb.200711167
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