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...
Main Authors: | , , , , , |
---|---|
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 |
_version_ | 1819227335312801792 |
---|---|
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. |
first_indexed | 2024-12-23T10:39:45Z |
format | Article |
id | doaj.art-483608b0e4d246cab67933410726fa5d |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-23T10:39:45Z |
publishDate | 2017-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT samuelmartinvilchez rhogtpaseregulatorsorchestratedistinctstagesofsynapticdevelopment AT leannawhitmore rhogtpaseregulatorsorchestratedistinctstagesofsynapticdevelopment AT hanneloreasmussen rhogtpaseregulatorsorchestratedistinctstagesofsynapticdevelopment AT jessicazareno rhogtpaseregulatorsorchestratedistinctstagesofsynapticdevelopment AT rickhorwitz rhogtpaseregulatorsorchestratedistinctstagesofsynapticdevelopment AT karennewelllitwa rhogtpaseregulatorsorchestratedistinctstagesofsynapticdevelopment |