title: miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling.
abstract: The small GTPase RhoG plays a central role in actin remodelling during diverse biological processes such as neurite outgrowth, cell migration, phagocytosis of apoptotic cells, and the invasion of pathogenic bacteria. Although it is known that RhoG stimulates neurite outgrowth in the rat pheochromocytoma PC12 cell line, neither the physiological function nor the regulation of this GTPase in neuronal differentiation is clear. Here, we identify RhoG as an inhibitor of neuronal process complexity, which is regulated by the microRNA miR-124. We find that RhoG inhibits dendritic branching in hippocampal neurons in vitro and in vivo. RhoG also inhibits axonal branching, acting via an ELMO/Dock180/Rac1 signalling pathway. However, RhoG inhibits dendritic branching dependent on the small GTPase Cdc42. Finally, we show that the expression of RhoG in neurons is suppressed by the CNS-specific microRNA miR-124 and connect the regulation of RhoG expression by miR-124 to the stimulation of neuronal process complexity. Thus, RhoG emerges as a cellular conductor of Rac1 and Cdc42 activity, in turn regulated by miR-124 to control axonal and dendritic branching.
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Franke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Sascha
authors.initials: S
authors.lastname: Johannes
authors.forename: Jan
authors.initials: J
authors.lastname: Baumgart
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C493871:DOCK180 protein, rat; C515800:ELMO1 protein, rat; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; C489578:Rhog protein, rat; D020558:GTP Phosphohydrolases; C499134:Rac1 protein, rat; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein