title: Rho-GTPase-activating protein interacting with Cdc-42-interacting protein 4 homolog 2 (Rich2): a new Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-activating protein that controls dendritic spine morphogenesis.
abstract: Development of dendritic spines is important for synaptic function, and alteration in spine morphogenesis is often associated with mental disorders. Rich2 was an uncharacterized Rho-GAP protein. Here we searched for a role of this protein in spine morphogenesis. We found that it is enriched in dendritic spines of cultured hippocampal pyramidal neurons during early stages of development. Rich2 specifically stimulated the Rac1 GTPase in these neurons. Inhibition of Rac1 by EHT 1864 increased the size and decreased the density of dendritic spines. Similarly, Rich2 overexpression increased the size and decreased the density of dendritic spines, whereas knock-down of the protein by specific si-RNA decreased both size and density of spines. The morphological changes were reflected by the increased amplitude and decreased frequency of miniature EPSCs induced by Rich2 overexpression, while si-RNA treatment decreased both amplitude and frequency of these events. Finally, treatment of neurons with EHT 1864 rescued the phenotype induced by Rich2 knock-down. These results suggested that Rich2 controls dendritic spine morphogenesis and function via inhibition of Rac1.
authors.affiliation: From CNRS, UMR-5203, Institut de Génomique Fonctionnelle, F-34000 Montpellier, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Raynaud
authors.forename: Enora
authors.initials: E
authors.lastname: Moutin
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmidt
authors.forename: Janine
authors.initials: J
authors.lastname: Dahl
authors.forename: Federica
authors.initials: F
authors.lastname: Bertaso
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.forename: Vincent
authors.initials: V
authors.lastname: Homburger
authors.forename: Laurent
authors.initials: L
authors.lastname: Fagni
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000201:enzymology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D061251:Primary Cell Culture; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: Glutamate; Morphogenesis; Rac1; Rho GTPases; Synapses