title: RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development.
abstract: 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.
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Martin-Vilchez
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Leanna
authors.initials: L
authors.lastname: Whitmore
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Asmussen
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zareno
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Rick
authors.initials: R
authors.lastname: Horwitz
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.|Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Newell-Litwa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D051381:Rats; D013569:Synapses / Q000201:enzymology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020742:rhoA GTP-Binding Protein