Role of fast cycling RhoD GTPase in neuronal polarity and development

CHUNGARA C; QUASSOLLO G; MARTÍN J; SOSA L; BISBAL M

Santa Cruz

Workshop; 2023 IUBMB EMBO Workshop Emerging Concepts of the Neuronal Cytoskeleton; 2023

IUBMB y EMBO

Rho GTPases are a family of monomeric small signaling G proteins involved in the regulation of manycellular processes, including cell migration, cell polarity and cell cycling progression. One of the lessstudied members of this family is RhoD, the only Rho GTPase to be expressed exclusively inmammals. RhoD has the particularity of having increased intrinsic GDP/GTP exchange activity.Available data suggest RhoD has unique impacts on cytoskeletal reorganization, endosome dynamicsand anterograde membrane trafficking, with signaling pathways and effectors distinct from thoseobserved for typical Rho GTPases. Although, information about the activity and function of this proteinin neuronal cell biology is limited, preliminary results of our lab propose an important role of RhoD atleast in neuronal differentiation. Based on the above, the aim of this study is to obtain new data ofRhoD activity and function in neuronal polarity and development. In order to study spatio-temporalactivation patterns of RhoD activity, we successfully develop and characterize a fluorescenceresonance energy transfer (FRET) biosensor that will be used in our neuronal systems. Furthermore,expression of RhoD activity mutants alters neuritic outgrowth and development in cultured hippocampalneurons as well as neuronal migration during cortical development in situ. In addition, using plasmamembrane protein fused to GTP and engineered with reversible aggregation domains, we observe thatexpression of dominant negative RhoD mutant delays the anterograde trafficking of post-Golgi plasmamembrane protein carriers. Altogether, our data suggest that RhoD plays an important role in neuronaldevelopment and neuritic outgrowth.