RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.

Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific st...

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Main Authors: Samuel Martin-Vilchez, Leanna Whitmore, Hannelore Asmussen, Jessica Zareno, Rick Horwitz, Karen Newell-Litwa
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5256999?pdf=render
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author Samuel Martin-Vilchez
Leanna Whitmore
Hannelore Asmussen
Jessica Zareno
Rick Horwitz
Karen Newell-Litwa
author_facet Samuel Martin-Vilchez
Leanna Whitmore
Hannelore Asmussen
Jessica Zareno
Rick Horwitz
Karen Newell-Litwa
author_sort Samuel Martin-Vilchez
collection DOAJ
description Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later maturation. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine precursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation. However, in later development, a novel Rac1 GAP, ARHGAP23, and RhoGDIs inactivate actomyosin dynamics to stabilize mature synapses. Our observations demonstrate that specific combinations of RhoGTPase regulatory proteins temporally balance RhoGTPase activity during post-synaptic spine development.
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spelling doaj.art-483608b0e4d246cab67933410726fa5d2022-12-21T17:50:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e017046410.1371/journal.pone.0170464RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.Samuel Martin-VilchezLeanna WhitmoreHannelore AsmussenJessica ZarenoRick HorwitzKaren Newell-LitwaSmall RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later maturation. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine precursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation. However, in later development, a novel Rac1 GAP, ARHGAP23, and RhoGDIs inactivate actomyosin dynamics to stabilize mature synapses. Our observations demonstrate that specific combinations of RhoGTPase regulatory proteins temporally balance RhoGTPase activity during post-synaptic spine development.http://europepmc.org/articles/PMC5256999?pdf=render
spellingShingle Samuel Martin-Vilchez
Leanna Whitmore
Hannelore Asmussen
Jessica Zareno
Rick Horwitz
Karen Newell-Litwa
RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
PLoS ONE
title RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
title_full RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
title_fullStr RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
title_full_unstemmed RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
title_short RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
title_sort rhogtpase regulators orchestrate distinct stages of synaptic development
url http://europepmc.org/articles/PMC5256999?pdf=render
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