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Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1
The dynamic assembly of filamentous (F) actin plays essential roles in the assembly of presynaptic boutons, the fusion, mobilization and recycling of synaptic vesicles (SVs), and presynaptic forms of plasticity. However, the molecular mechanisms that regulate the temporal and spatial assembly of pre...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405365/ https://www.ncbi.nlm.nih.gov/pubmed/25897839 http://dx.doi.org/10.1371/journal.pone.0120093 |
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author | Wagh, Dhananjay Terry-Lorenzo, Ryan Waites, Clarissa L. Leal-Ortiz, Sergio A. Maas, Christoph Reimer, Richard J. Garner, Craig C. |
author_facet | Wagh, Dhananjay Terry-Lorenzo, Ryan Waites, Clarissa L. Leal-Ortiz, Sergio A. Maas, Christoph Reimer, Richard J. Garner, Craig C. |
author_sort | Wagh, Dhananjay |
collection | PubMed |
description | The dynamic assembly of filamentous (F) actin plays essential roles in the assembly of presynaptic boutons, the fusion, mobilization and recycling of synaptic vesicles (SVs), and presynaptic forms of plasticity. However, the molecular mechanisms that regulate the temporal and spatial assembly of presynaptic F-actin remain largely unknown. Similar to other F-actin rich membrane specializations, presynaptic boutons contain a set of molecules that respond to cellular cues and trans-synaptic signals to facilitate activity-dependent assembly of F-actin. The presynaptic active zone (AZ) protein Piccolo has recently been identified as a key regulator of neurotransmitter release during SV cycling. It does so by coordinating the activity-dependent assembly of F-Actin and the dynamics of key plasticity molecules including Synapsin1, Profilin and CaMKII. The multidomain structure of Piccolo, its exquisite association with the AZ, and its ability to interact with a number of actin-associated proteins suggest that Piccolo may function as a platform to coordinate the spatial assembly of F-actin. Here we have identified Daam1, a Formin that functions with Profilin to drive F-actin assembly, as a novel Piccolo binding partner. We also found that within cells Daam1 activation promotes Piccolo binding, an interaction that can spatially direct the polymerization of F-Actin. Moreover, similar to Piccolo and Profilin, Daam1 loss of function impairs presynaptic-F-actin assembly in neurons. These data suggest a model in which Piccolo directs the assembly of presynaptic F-Actin from the AZ by scaffolding key actin regulatory proteins including Daam1. |
format | Online Article Text |
id | pubmed-4405365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44053652015-05-07 Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 Wagh, Dhananjay Terry-Lorenzo, Ryan Waites, Clarissa L. Leal-Ortiz, Sergio A. Maas, Christoph Reimer, Richard J. Garner, Craig C. PLoS One Research Article The dynamic assembly of filamentous (F) actin plays essential roles in the assembly of presynaptic boutons, the fusion, mobilization and recycling of synaptic vesicles (SVs), and presynaptic forms of plasticity. However, the molecular mechanisms that regulate the temporal and spatial assembly of presynaptic F-actin remain largely unknown. Similar to other F-actin rich membrane specializations, presynaptic boutons contain a set of molecules that respond to cellular cues and trans-synaptic signals to facilitate activity-dependent assembly of F-actin. The presynaptic active zone (AZ) protein Piccolo has recently been identified as a key regulator of neurotransmitter release during SV cycling. It does so by coordinating the activity-dependent assembly of F-Actin and the dynamics of key plasticity molecules including Synapsin1, Profilin and CaMKII. The multidomain structure of Piccolo, its exquisite association with the AZ, and its ability to interact with a number of actin-associated proteins suggest that Piccolo may function as a platform to coordinate the spatial assembly of F-actin. Here we have identified Daam1, a Formin that functions with Profilin to drive F-actin assembly, as a novel Piccolo binding partner. We also found that within cells Daam1 activation promotes Piccolo binding, an interaction that can spatially direct the polymerization of F-Actin. Moreover, similar to Piccolo and Profilin, Daam1 loss of function impairs presynaptic-F-actin assembly in neurons. These data suggest a model in which Piccolo directs the assembly of presynaptic F-Actin from the AZ by scaffolding key actin regulatory proteins including Daam1. Public Library of Science 2015-04-21 /pmc/articles/PMC4405365/ /pubmed/25897839 http://dx.doi.org/10.1371/journal.pone.0120093 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Wagh, Dhananjay Terry-Lorenzo, Ryan Waites, Clarissa L. Leal-Ortiz, Sergio A. Maas, Christoph Reimer, Richard J. Garner, Craig C. Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 |
title | Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 |
title_full | Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 |
title_fullStr | Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 |
title_full_unstemmed | Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 |
title_short | Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1 |
title_sort | piccolo directs activity dependent f-actin assembly from presynaptic active zones via daam1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405365/ https://www.ncbi.nlm.nih.gov/pubmed/25897839 http://dx.doi.org/10.1371/journal.pone.0120093 |
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