Overexpression of constitutively active forms of small gtpases of the rho family modify neuronal morphology.

Ortiz, C. ^{1, 2} , Ruiz, A. ^{1, 2} , Llavero, F. ^{2, 3} , Matute, C. ^{1, 2} , Zugaza, J. ^{2, 3} & Alberdi, E. ^{1, 2}

1 Departamento de Neurociencias, Facultad de Medicina y Odontología
2 Achucarro Basque Center for Neuroscience
3 Departamento de Genética, Antropología Física y Fisiología, Facultad de Ciencia y Tecnología. Universidad del País Vasco / Euskal Herriko Unibertsitatea.

Small GTPases of the Rho family are key players in complex signaling networks that control normal activity in most if not all cell types. Like other small GTPases, Rho GTPases function as molecular switches to control celular signaling pathways. They are present in two conformations, an inactive and other active. In their active configuration, GTPases of the Rho family are best known for controlling the appropriate actin cytoskeleton reorganization in response to extracellular signals, although their implication in additional biological processes, such as gene expression regulation, cell polarity and cell migration have also been reported. Functional specificity of small GTPases of the Rho family in intracellular signaling pathways depends mainly on the cellular system, type of stimuli and their intracellular localization. Regarding the nervous system, small GTPases of the Rho family participate actively controlling cytoskeleton dynamics in neurons, thereby modulating synaptic plasticity. We have explored the effect produced by the overexpression of the constitutively active forms of RhoA, Rac1 and Cdc42 on the actin cytoskeleton in primary neurons. After 5, 10, 15 y 17 DIVs, we have observed that the overexpression of RhoA and Cdc42 produce a dramatic contraction of dendrites and axons, causing a rounding of the neurons. Unlike the RhoA, Cdc42 induces the formation of an actin pericellular structure whose appearance resembles a combination of filli-lamellipodia. In addition, Cdc42 induces an unusual repositioning of the cell nucleus. However and in contrast to RhoA and Cdc42, overexpression of constitutively active Rac progressively leads to neuronal death.

Supported by CIBERNED, Gobierno Vasco and MINECO