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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Bibliographic Details
Published in:PloS one 2017-01, Vol.12 (1), p.e0170464-e0170464
Main Authors: Martin-Vilchez, Samuel, Whitmore, Leanna, Asmussen, Hannelore, Zareno, Jessica, Horwitz, Rick, Newell-Litwa, Karen
Format: Article
Language:English
Subjects:
Actin
Actomyosin
Animals
Autism
Biology
Biology and Life Sciences
Cdc42 protein
Cells, Cultured
Developmental stages
Elongation
GTPases
Hippocampus - cytology
Hippocampus - enzymology
Intellectual disabilities
Learning
Maturation
Medicine
Medicine and Health Sciences
Memory
Morphogenesis
Morphology
Muscle proteins
Mutation
Neurons
Physiological aspects
Polymerization
Proteins
Rac1 protein
Rats
Regulation
Regulatory proteins
Research and Analysis Methods
rhoA GTP-Binding Protein - metabolism
RhoA protein
Spine
Synapses
Synapses - enzymology
Synaptic density
Synaptic transmission
Synaptogenesis
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0170464