Cellular and Molecular Neurobiology
Author: CLARA INES CHUNGARA | email: cchungara@immf.uncor.edu
Clara Inés Chungara 1°, Gonzalo Quassollo 1°, Josefina Inés Martín 1°, Mariano Bisbal 1°
1° Institute of Medical Research Mercedes and Martin Ferreyra. Friuli 2434 – INIMEC – CONICET – UNC. Córdoba – Argentina
Neurons are highly polarized cells typically extending a long thin axon and multiple short branched dendrites. This compartmentalization requires specific cytoskeletal dynamics events, including actin and microtubules cytoskeleton assembly, and the addition of membranes in neuron specialized regions. Most of them are highly regulated by several small Rho GTPases with their specific effectors. Even though most studies have been focused on the canonical Rho GTPases RhoA, Rac1 and Cdc42, other less studied members of this family like RhoD suggest to have unique effects on cytoskeleton and membrane dynamics. RhoD is the only Rho GTPase to be expressed exclusively in mammals and has a higher intrinsic GTP exchange activity. In order to study spatio-temporal activation patterns of RhoD activity, we successfully develop and characterize a fluorescence resonance energy transfer (FRET)-based biosensor that will be used in our neuronal systems. Furthermore, expression of RhoD activity mutants alters neuritic outgrowth and development in cultured hippocampal neurons as well as neuronal migration during cortical development in situ. In addition, using a state-of-the-art system to synchronize the secretory pathway, we observe that the expression of a dominant negative RhoD mutant induces a delay in the anterograde trafficking of post-Golgi plasma membrane protein carriers. Altogether, our data suggest that RhoD plays an important role in neuronal development and neuritic outgrowth.