RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development
| Autor: | Karen Newell-Litwa, Leanna Whitmore, Hannelore Asmussen, Jessica Zareno, Rick Horwitz, Samuel Martin-Vilchez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RHOA Physiology lcsh:Medicine CDC42 Hippocampus Nervous System Fluorophotometry Signaling Molecules Spectrum Analysis Techniques Cell Signaling Animal Cells Spine morphology Medicine and Health Sciences Fluorescence Resonance Energy Transfer Guanine Nucleotide Exchange Factors Deletions lcsh:Science Cells Cultured Neurons Multidisciplinary biology Chromosome Biology Duplications 3. Good health Cell biology Chromosomal Aberrations Electrophysiology Spectrophotometry Cellular Types Anatomy Research Article Signal Transduction Neurophysiology RAC1 Research and Analysis Methods 03 medical and health sciences Developmental Neuroscience Animals Actin Activator (genetics) lcsh:R Biology and Life Sciences Cell Biology Neuronal Dendrites Rats 030104 developmental biology Cellular Neuroscience Synapses biology.protein lcsh:Q rhoA GTP-Binding Protein Neuroscience |
| Zdroj: | PLoS ONE, Vol 12, Iss 1, p e0170464 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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