015 | Role of Rho GTPase RhoD in neuronal development

Cellular and Molecular Neurobiology

Author: CLARA INÉS CHUNGARA | Email: cchungara@immf.uncor.edu

Clara Inés Chungara , Gonzalo Quassollo , Josefina Martín , Mariano Bisbal

1° Instituto de Investigación Médica Mercedes y Martín Ferreyra

Rho GTPases are small signaling proteins of the RAS superfamily. One of the less studied members of this family is RhoD, the only Rho GTPase to be expressed exclusively in mammals. RhoD has the particularity of having increased intrinsic GDP/GTP exchange activity. Available data suggest RhoD plays an important role in the organization and regulation of actin cytoskeleton dynamics and Golgi apparatus homeostasis. Although information about the activity, regulation and function of this protein in neuronal cell biology is limited, results of our lab propose an important role of RhoD at least in neuronal differentiation. Based on the above, the aim of this study is to obtain new data of RhoD activity and function in neuronal polarity and development. In order to study spatio-temporal activation patterns of RhoD activity, we develop and characterize a FRET-based biosensor that will be used in our neuronal systems. Furthermore, the down-regulation of endogenous RhoD by an shRNAi generated in our lab, alters neuritic outgrowth and development in cultured 2 and 10 d.i.v. hippocampal neurons. As well, RhoD negative mutant expressions decreased neuronal complexity. Moreover, using plasma membrane protein engineered with reversible aggregation domains, we observe that expression of RhoD negative mutant delays the anterograde trafficking of post-Golgi plasma membrane protein carriers. These data suggest RhoD plays an important role during neuronal differentiation and neuritic outgrowth.