Cellular and Molecular Neurobiology
Author: CLARA INÉS CHUNGARA | Email: cchungara@immf.uncor.edu
Clara Ines Chungara1°, Gonzalo Quassollo1°, Josefina Martín1°, Mariano Bisbal1°
1° Institute of Medical Research Mercedes and Martin Ferreyra (CONICET- UNC- IMMF) (5016) Córdoba. Argentina
Neurons are highly polarized cells with long axons and multiple dendrites, essential for processing and transmitting electrical signals. The establishment and maintenance of neuronal polarity involve processes such as actin and microtubule cytoskeleton assembly, membrane protein trafficking, and vesicle transport from the Golgi apparatus (GA). Rho GTPases regulate neuronal cytoskeleton by controlling actin filament dynamics. RhoD, a less characterized member of this family, expressed exclusively in mammals, plays unique roles in cytoskeletal dynamics and organelle function. RhoD exhibits increased intrinsic GDP/GTP exchange activity and is involved in organizing the actin cytoskeleton and maintaining GA homeostasis. Our research suggests that RhoD is crucial for neuronal differentiation, influencing neuritic outgrowth and post-GA membrane protein trafficking. To investigate RhoD’s role in neuronal polarity, we developed a FRET-biosensor for spatio-temporal activation studies. Down-regulation of RhoD via shRNAi in cultured hippocampal neurons led to altered neurite outgrowth and reduced neuronal complexity. In addition, expression of a RhoD- negative activity mutant delayed anterograde trafficking of post-GA plasma membrane proteins, underscoring RhoD’s importance in cytoskeletal dynamics and neuronal development. These findings highlight RhoD’s critical role in maintaining neuronal polarity and suggest broader implications for neuronal architecture.